rs748601665

Variant names:

• chr16-56669892-C-G
• rs748601665
• NM_005951.2:c.8C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-56669892-C-G
• chr16-56669892-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005951.2(MT1H):​c.8C>G​(p.Pro3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MT1H NM_005951.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.255449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1H	NM_005951.2	c.8C>G	p.Pro3Arg	missense_variant	Exon 1 of 3	ENST00000332374.5	NP_005942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1H	ENST00000332374.5	c.8C>G	p.Pro3Arg	missense_variant	Exon 1 of 3	1	NM_005951.2	ENSP00000330587.5
MT1H	ENST00000569155.1	c.8C>G	p.Pro3Arg	missense_variant	Exon 1 of 2	1		ENSP00000457114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.81	T;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		1.0	D;.
Vest4		0.34
MutPred		0.60		Gain of phosphorylation at S6 (P = 0.1295);Gain of phosphorylation at S6 (P = 0.1295);
MVP		0.092
MPC		0.013
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.38
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs748601665; hg19: chr16-56703804;