16-56669892-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005951.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1H	NM_005951.2	MANE Select	c.8C>G	p.Pro3Arg	missense	Exon 1 of 3	NP_005942.1	P80294

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1H	ENST00000332374.5	TSL:1 MANE Select	c.8C>G	p.Pro3Arg	missense	Exon 1 of 3	ENSP00000330587.5	P80294
	MT1H	ENST00000569155.1	TSL:1	c.8C>G	p.Pro3Arg	missense	Exon 1 of 2	ENSP00000457114.1	H3BTC4
	MT1H	ENST00000868220.1		c.8C>G	p.Pro3Arg	missense	Exon 1 of 2	ENSP00000538279.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.8
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.60		Gain of phosphorylation at S6 (P = 0.1295)
MVP		0.092
MPC		0.013
ClinPred		0.99	D
GERP RS		2.0
PromoterAI		0.0091	Neutral
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

Other links and lift over

dbSNP: rs748601665; hg19: chr16-56703804;