Variant 16-56652603-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_005947.3(MT1B):c.61T>G(p.Cys21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MT1B
NM_005947.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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:

ENSG00000259923 (HGNC:):

ENSG00000259923 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity MT1B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28636858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1B	NM_005947.3 linkuse as main transcript	c.61T>G	p.Cys21Gly	missense_variant	2/3	ENST00000334346.3	NP_005938.1	P07438

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MT1B	ENST00000334346.3 linkuse as main transcript	c.61T>G	p.Cys21Gly	missense_variant	2/3	1	NM_005947.3	ENSP00000334998.2	P07438
MT1B	ENST00000562399.1 linkuse as main transcript	c.61T>G	p.Cys21Gly	missense_variant	2/3	3		ENSP00000456056.1	H3BR34
ENSG00000259923	ENST00000568608.1 linkuse as main transcript	n.211T>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251486

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000269

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000821

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

Sep 03, 2024

The c.61T>G (p.C21G) alteration is located in exon 2 (coding exon 2) of the MT1B gene. This alteration results from a T to G substitution at nucleotide position 61, causing the cysteine (C) at amino acid position 21 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.41

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

-0.0036

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-10

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

0.99

D;.

Vest4

0.51

MVP

0.040

MPC

0.46

ClinPred

0.32

GERP RS

2.6

Varity_R

0.86

gMVP

0.58

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over