rs2062546

Variant names:

• chr16-56670305-T-A
• rs2062546
• NM_005951.2:c.29-201T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56670305-T-A
• chr16-56670305-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005951.2(MT1H):​c.29-201T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,060 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.069 (650 hom., cov: 33)
• Consequence: MT1H NM_005951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

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.29-201T>A		intron	N/A	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.29-201T>A		intron	N/A	ENSP00000330587.5	P80294
	MT1H	ENST00000569155.1	TSL:1	c.29-201T>A		intron	N/A	ENSP00000457114.1	H3BTC4
	MT1H	ENST00000868220.1		c.28+393T>A		intron	N/A	ENSP00000538279.1

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10452 AN: 151942 Hom.: 647 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0793

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0688 AC: 10459 AN: 152060 Hom.: 650 Cov.: 33 AF XY: 0.0726 AC XY: 5396 AN XY: 74366

African (AFR) AF: 0.0160 AC: 663 AN: 41376

American (AMR) AF: 0.174 AC: 2662 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 297 AN: 3472

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5172

South Asian (SAS) AF: 0.127 AC: 612 AN: 4812

European-Finnish (FIN) AF: 0.0332 AC: 353 AN: 10620

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0628 AC: 4270 AN: 68010

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0257 Hom.: 17

Bravo AF: 0.0767

Asia WGS AF: 0.168 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		-0.071
PromoterAI		0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2062546;

hg19: chr16-56704217;

COSMIC: COSV60090838;

COSMIC: COSV60090838;