16-56666887-A-G

Variant names:

• chr16-56666887-A-G
• NM_001301267.2:c.181T>C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_001301267.2(MT1G):​c.181T>C​(p.Cys61Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MT1G NM_001301267.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10

Genes affected

MT1G (HGNC:7399): (metallothionein 1G) Enables zinc ion binding activity. Involved in cellular response to metal ion; cellular response to vascular endothelial growth factor stimulus; and negative regulation of growth. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity MT1G_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1G	NM_001301267.2	c.181T>C	p.Cys61Arg	missense_variant	Exon 3 of 3	ENST00000379811.4	NP_001288196.1
MT1G	NM_005950.3	c.178T>C	p.Cys60Arg	missense_variant	Exon 3 of 3		NP_005941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1G	ENST00000379811.4	c.181T>C	p.Cys61Arg	missense_variant	Exon 3 of 3	1	NM_001301267.2	ENSP00000369139.4
MT1G	ENST00000444837.6	c.178T>C	p.Cys60Arg	missense_variant	Exon 3 of 3	1		ENSP00000391397.2
MT1G	ENST00000568675.1	n.547T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
MT1G	ENST00000569500.5	c.112T>C	p.Cys38Arg	missense_variant	Exon 2 of 2	3		ENSP00000456675.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178T>C (p.C60R) alteration is located in exon 3 (coding exon 3) of the MT1G gene. This alteration results from a T to C substitution at nucleotide position 178, causing the cysteine (C) at amino acid position 60 to be replaced by an arginine (R). 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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	.;.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;T;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-1.1	T
PROVEAN	Pathogenic	-9.3	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.95	P;.;.
Vest4		0.86
MutPred		0.60		Gain of solvent accessibility (P = 0.0133);.;.;
MVP		0.13
MPC		0.0014
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.90
gMVP		0.33

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: chr16-56700799;