16-56670921-G-C

Position:

• chr16-56670921-G-C

Variant summary

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

The NM_005951.2(MT1H):​c.118G>C​(p.Gly40Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MT1H NM_005951.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

MT1H (HGNC:7400): (metallothionein 1H) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion and cellular response to zinc ion. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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
MT1H	NM_005951.2	c.118G>C	p.Gly40Arg	missense_variant	3/3	ENST00000332374.5	NP_005942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1H	ENST00000332374.5	c.118G>C	p.Gly40Arg	missense_variant	3/3	1	NM_005951.2	ENSP00000330587.5
MT1H	ENST00000569155.1	c.*186G>C		3_prime_UTR_variant	2/2	1		ENSP00000457114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Mar 07, 2023

The c.118G>C (p.G40R) alteration is located in exon 3 (coding exon 3) of the MT1H gene. This alteration results from a G to C substitution at nucleotide position 118, causing the glycine (G) at amino acid position 40 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.057
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.059	T
Polyphen		0.70	P
Vest4		0.60
MutPred		0.64		Loss of ubiquitination at K43 (P = 0.0271);
MVP		0.048
MPC		0.013
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.73
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr16-56704833;