Variant rs61744104 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_005947.3(MT1B):c.56G>C(p.Cys19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,613,984 control chromosomes in the GnomAD database, including 43 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 0.0063 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 37 hom. )

Consequence

MT1B
NM_005947.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

MT1B (HGNC:7394): (metallothionein 1B) The protein encoded by this gene binds heavy metals and protects against toxicity from heavy metal ions. This gene is found in a cluster of similar genes on chromosome 16. [provided by RefSeq, Jul 2016]

MT1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity MT1B_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.007817745).

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1B	NM_005947.3 linkuse as main transcript	c.56G>C	p.Cys19Ser	missense_variant	2/3	ENST00000334346.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1B	ENST00000334346.3 linkuse as main transcript	c.56G>C	p.Cys19Ser	missense_variant	2/3	1	NM_005947.3	P1
MT1B	ENST00000562399.1 linkuse as main transcript	c.56G>C	p.Cys19Ser	missense_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

954

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00463

AC:

1165

AN:

251486

Hom.:

AF XY:

0.00471

AC XY:

640

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00960

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.00610

Gnomad NFE exome

AF:

0.00518

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00542

AC:

7926

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

3918

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00902

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00435

Gnomad4 FIN exome

AF:

0.00674

Gnomad4 NFE exome

AF:

0.00567

Gnomad4 OTH exome

AF:

0.00550

GnomAD4 genome

AF:

0.00627

AC:

955

AN:

152314

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00593

Gnomad4 NFE

AF:

0.00515

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00502

Hom.:

Bravo

AF:

0.00632

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00569

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00446

AC:

541

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.69

DEOGEN2

Benign

0.36

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.0047

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.61

T;D

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.75

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-9.3

D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.97

D;.

Vest4

0.49

MutPred

0.69

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.055

MPC

0.46

ClinPred

0.13

GERP RS

2.6

Varity_R

0.69

gMVP

0.46

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