Variant 16-56652974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005947.3(MT1B):c.95G>A(p.Cys32Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000434 in 1,612,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

MT1B
NM_005947.3 missense, splice_region

Scores

Splicing: ADA: 0.1157

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082736164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1B	NM_005947.3 linkuse as main transcript	c.95G>A	p.Cys32Tyr	missense_variant, splice_region_variant	3/3	ENST00000334346.3	NP_005938.1	P07438

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1B	ENST00000334346.3 linkuse as main transcript	c.95G>A	p.Cys32Tyr	missense_variant, splice_region_variant	3/3	1	NM_005947.3	ENSP00000334998.2		P07438
MT1B	ENST00000562399.1 linkuse as main transcript	c.93G>A	p.Lys31Lys	splice_region_variant, synonymous_variant	3/3	3		ENSP00000456056.1		H3BR34

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251374

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460770

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000263

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000955

Bravo

AF:

0.000578

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.95G>A (p.C32Y) alteration is located in exon 3 (coding exon 3) of the MT1B gene. This alteration results from a G to A substitution at nucleotide position 95, causing the cysteine (C) at amino acid position 32 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.014

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.57

REVEL

Benign

0.077

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.035

Polyphen

0.0

Vest4

0.16

MutPred

0.46

Gain of sheet (P = 0.0827);

MVP

0.030

MPC

0.12

ClinPred

1.0

GERP RS

3.1

Varity_R

0.72

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.12

dbscSNV1_RF

Benign

0.32

SpliceAI score (max)

0.15

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