rs881144

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001374504.1(TMPRSS6):c.1227C>T(p.Tyr409Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,600 control chromosomes in the GnomAD database, including 10,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 667 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9337 hom. )

Consequence

TMPRSS6
NM_001374504.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.868

Publications

19 publications found

Variant links:

Genes affected

TMPRSS6 (HGNC:16517): (transmembrane serine protease 6) The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TMPRSS6 Gene-Disease associations (from GenCC):

IRIDA syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

TMPRSS6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-37075250-G-A is Benign according to our data. Variant chr22-37075250-G-A is described in ClinVar as Benign. ClinVar VariationId is 262720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.868 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1 link	c.1227C>T	p.Tyr409Tyr	synonymous_variant	Exon 11 of 18	ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1 link	c.1227C>T	p.Tyr409Tyr	synonymous_variant	Exon 11 of 18		NM_001374504.1	ENSP00000501573.1		Q8IU80-1

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12455

AN:

152172

Hom.:

665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0692

Gnomad ASJ

AF:

0.0746

Gnomad EAS

AF:

0.0431

Gnomad SAS

AF:

0.0379

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0869

GnomAD2 exomes

AF:

0.0893

AC:

22323

AN:

249996

AF XY:

0.0903

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.0524

Gnomad ASJ exome

AF:

0.0790

Gnomad EAS exome

AF:

0.0498

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.109

AC:

159533

AN:

1461310

Hom.:

9337

Cov.:

AF XY:

0.107

AC XY:

78029

AN XY:

726974

show subpopulations

African (AFR)

AF:

0.0176

AC:

590

AN:

33480

American (AMR)

AF:

0.0549

AC:

2454

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0809

AC:

2115

AN:

26136

East Asian (EAS)

AF:

0.0369

AC:

1463

AN:

39700

South Asian (SAS)

AF:

0.0435

AC:

3748

AN:

86258

European-Finnish (FIN)

AF:

0.140

AC:

7409

AN:

52860

Middle Eastern (MID)

AF:

0.0709

AC:

409

AN:

5768

European-Non Finnish (NFE)

AF:

0.122

AC:

135320

AN:

1111998

Other (OTH)

AF:

0.0998

AC:

6025

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9095

18189

27284

36378

45473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4764

9528

14292

19056

23820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0818

AC:

12462

AN:

152290

Hom.:

667

Cov.:

AF XY:

0.0819

AC XY:

6097

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0228

AC:

948

AN:

41582

American (AMR)

AF:

0.0691

AC:

1057

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0746

AC:

259

AN:

3472

East Asian (EAS)

AF:

0.0436

AC:

226

AN:

5186

South Asian (SAS)

AF:

0.0390

AC:

188

AN:

4826

European-Finnish (FIN)

AF:

0.149

AC:

1583

AN:

10592

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7961

AN:

68008

Other (OTH)

AF:

0.0865

AC:

183

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

610

1221

1831

2442

3052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0862

Hom.:

617

Bravo

AF:

0.0743

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.117

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcytic anemia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Iron-refractory iron deficiency anemia

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.10

(source)

DANN

Benign

0.88

PhyloP100

-0.87

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over