chr16-56633775-G-T

Position:

• chr16-56633775-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_176870.3(MT1M):​c.119G>T​(p.Gly40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MT1M NM_176870.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

Genes affected

MT1M (HGNC:14296): (metallothionein 1M) This gene encodes a member of the metallothionein superfamily, type 1 family. Metallothioneins have a high content of cysteine residues that bind various heavy metals. These genes are transcriptionally regulated by both heavy metals and glucocorticoids. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1M	NM_176870.3	c.119G>T	p.Gly40Val	missense_variant	3/3	ENST00000379818.4	NP_789846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1M	ENST00000379818.4	c.119G>T	p.Gly40Val	missense_variant	3/3	1	NM_176870.3	ENSP00000369146.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.119G>T (p.G40V) alteration is located in exon 3 (coding exon 3) of the MT1M gene. This alteration results from a G to T substitution at nucleotide position 119, causing the glycine (G) at amino acid position 40 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.88	P
Vest4		0.29
MutPred		0.56		Loss of loop (P = 0.0374);
MVP		0.33
MPC		0.087
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.86
gMVP		0.096

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-56667687;