Variant rs9934181 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005951.2(MT1H):c.49G>A(p.Gly17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,614,198 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 183 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 199 hom. )

Consequence

MT1H
NM_005951.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Variant links:

Genes affected

MT1H (HGNC:7400): (metallothionein 1H) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion and cellular response to zinc ion. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1H links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021295547).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1H	NM_005951.2 linkuse as main transcript	c.49G>A	p.Gly17Ser	missense_variant	2/3	ENST00000332374.5	NP_005942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1H	ENST00000332374.5 linkuse as main transcript	c.49G>A	p.Gly17Ser	missense_variant	2/3	1	NM_005951.2	ENSP00000330587	P1
MT1H	ENST00000569155.1 linkuse as main transcript	c.49G>A	p.Gly17Ser	missense_variant	2/2	1		ENSP00000457114

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4247

AN:

152204

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00781

AC:

1964

AN:

251428

Hom.:

AF XY:

0.00594

AC XY:

807

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0973

Gnomad AMR exome

AF:

0.00526

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00358

AC:

5235

AN:

1461876

Hom.:

199

Cov.:

AF XY:

0.00323

AC XY:

2349

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000973

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.0279

AC:

4256

AN:

152322

Hom.:

183

Cov.:

AF XY:

0.0268

AC XY:

1996

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0952

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.0315

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0939

AC:

413

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00949

AC:

1152

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.7

DANN

Benign

0.62

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.27

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.35

N;D

REVEL

Benign

0.027

Sift

Benign

0.47

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.029

B;.

Vest4

0.25

MVP

0.014

MPC

0.013

ClinPred

0.00085

GERP RS

1.5

Varity_R

0.029

gMVP

0.065

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over