Variant rs881144 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001374504.1(TMPRSS6):c.1227C>T(p.Tyr409=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1 linkuse as main transcript	c.1227C>T	p.Tyr409=	synonymous_variant	11/18	ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1 linkuse as main transcript	c.1227C>T	p.Tyr409=	synonymous_variant	11/18		NM_001374504.1	ENSP00000501573	P1	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

GnomAD3 exomes

AF:

0.0893

AC:

22323

AN:

249996

Hom.:

1178

AF XY:

0.0903

AC XY:

12226

AN XY:

135366

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 SAS exome

AF:

0.0422

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

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.0549

Gnomad4 ASJ exome

AF:

0.0809

Gnomad4 EAS exome

AF:

0.0369

Gnomad4 SAS exome

AF:

0.0435

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.0998

GnomAD4 genome

AF:

0.0818

AC:

12462

AN:

152290

Hom.:

667

Cov.:

AF XY:

0.0819

AC XY:

6097

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.0691

Gnomad4 ASJ

AF:

0.0746

Gnomad4 EAS

AF:

0.0436

Gnomad4 SAS

AF:

0.0390

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0865

Alfa

AF:

0.0926

Hom.:

553

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Microcytic anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.10

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over