Variant 22-37084229-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000442782.7(TMPRSS6):c.1262T>C(p.Ile421Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,329,838 control chromosomes in the GnomAD database, including 39,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5438 hom., cov: 29)

Exomes 𝑓: 0.24 ( 34445 hom. )

Consequence

TMPRSS6
ENST00000442782.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.812

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025805533).

BP6

Variant 22-37084229-A-G is Benign according to our data. Variant chr22-37084229-A-G is described in ClinVar as [Benign]. Clinvar id is 1261467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 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.1196+66T>C		intron_variant		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.1196+66T>C		intron_variant			NM_001374504.1	ENSP00000501573.1		Q8IU80-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

39069

AN:

148056

Hom.:

5429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.0980

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.223

AC:

40819

AN:

182858

Hom.:

4904

AF XY:

0.222

AC XY:

21427

AN XY:

96704

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.190

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.241

AC:

284487

AN:

1181636

Hom.:

34445

Cov.:

AF XY:

0.239

AC XY:

142042

AN XY:

594082

show subpopulations

Gnomad4 AFR exome

AF:

0.375

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.264

AC:

39119

AN:

148202

Hom.:

5438

Cov.:

AF XY:

0.263

AC XY:

18959

AN XY:

72204

show subpopulations

Gnomad4 AFR

AF:

0.353

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.228

Hom.:

1970

Bravo

AF:

0.259

TwinsUK

AF:

0.229

AC:

849

ALSPAC

AF:

0.244

AC:

940

ExAC

AF:

0.197

AC:

23221

Asia WGS

AF:

0.211

AC:

736

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.28

DANN

Benign

0.48

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.93

REVEL

Benign

0.053

Sift

Benign

0.16

Sift4G

Benign

0.21

Vest4

0.028

ClinPred

0.00040

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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