rs2235321

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001374504.1(TMPRSS6):c.2190C>T(p.Tyr730=) variant causes a synonymous change. The variant allele was found at a frequency of 0.378 in 1,613,618 control chromosomes in the GnomAD database, including 117,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11343 hom., cov: 33)

Exomes 𝑓: 0.38 ( 106165 hom. )

Consequence

TMPRSS6
NM_001374504.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.74

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 22-37066886-G-A is Benign according to our data. Variant chr22-37066886-G-A is described in ClinVar as [Benign]. Clinvar id is 262726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37066886-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS6	NM_001374504.1 linkuse as main transcript	c.2190C>T	p.Tyr730=	synonymous_variant	17/18	ENST00000676104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS6	ENST00000676104.1 linkuse as main transcript	c.2190C>T	p.Tyr730=	synonymous_variant	17/18		NM_001374504.1	P1	Q8IU80-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58137

AN:

151890

Hom.:

11330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.360

AC:

90277

AN:

250550

Hom.:

16899

AF XY:

0.359

AC XY:

48723

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.442

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.377

AC:

551480

AN:

1461610

Hom.:

106165

Cov.:

AF XY:

0.375

AC XY:

272372

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.478

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.383

AC:

58180

AN:

152008

Hom.:

11343

Cov.:

AF XY:

0.381

AC XY:

28328

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.478

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.360

Alfa

AF:

0.364

Hom.:

16458

Bravo

AF:

0.374

Asia WGS

AF:

0.290

AC:

1008

AN:

3478

EpiCase

AF:

0.381

EpiControl

AF:

0.368

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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

-0.45

Cadd

Benign

7.4

Dann

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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