Variant 22-37084757-C-T 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.1056G>A(p.Ser352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,564,542 control chromosomes in the GnomAD database, including 90,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9173 hom., cov: 32)

Exomes 𝑓: 0.34 ( 81511 hom. )

Consequence

TMPRSS6
NM_001374504.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.67

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=-0.53).

BP6

Variant 22-37084757-C-T is Benign according to our data. Variant chr22-37084757-C-T is described in ClinVar as [Benign]. Clinvar id is 262719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 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.1056G>A	p.Ser352=	synonymous_variant	9/18	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.1056G>A	p.Ser352=	synonymous_variant	9/18		NM_001374504.1	ENSP00000501573	P1	Q8IU80-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52029

AN:

151832

Hom.:

9174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.312

AC:

55328

AN:

177408

Hom.:

9007

AF XY:

0.311

AC XY:

29153

AN XY:

93890

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.337

AC:

475763

AN:

1412592

Hom.:

81511

Cov.:

AF XY:

0.335

AC XY:

233597

AN XY:

697920

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.343

AC:

52046

AN:

151950

Hom.:

9173

Cov.:

AF XY:

0.344

AC XY:

25561

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.410

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.333

Hom.:

16868

Bravo

AF:

0.334

Asia WGS

AF:

0.236

AC:

818

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.48

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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