rs8051405

Variant names:

• chr16-56683684-G-A
• rs8051405
• NM_005952.4:c.95-274G>A

Variant summary

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

The NM_005952.4(MT1X):​c.95-274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 467,946 control chromosomes in the GnomAD database, including 38,577 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 0.39 (11565 hom., cov: 32)
  • Exomes 𝑓: 0.41 (27012 hom.)
• Consequence: MT1X NM_005952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 7 publications found

Genes affected

MT1X (HGNC:7405): (metallothionein 1X) Predicted to enable copper ion binding activity and zinc ion binding activity. Involved in cellular response to cadmium ion; cellular response to erythropoietin; and cellular response to zinc ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259827 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1X	NM_005952.4	c.95-274G>A		intron_variant	Intron 2 of 2	ENST00000394485.5	NP_005943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1X	ENST00000394485.5	c.95-274G>A		intron_variant	Intron 2 of 2	1	NM_005952.4	ENSP00000377995.4

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58683 AN: 151944 Hom.: 11553 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.408 AC: 128837 AN: 315884 Hom.: 27012 Cov.: 4 AF XY: 0.403 AC XY: 66978 AN XY: 166266

African (AFR) AF: 0.321 AC: 2878 AN: 8978

American (AMR) AF: 0.344 AC: 3842 AN: 11180

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 4409 AN: 9872

East Asian (EAS) AF: 0.504 AC: 9732 AN: 19328

South Asian (SAS) AF: 0.320 AC: 10272 AN: 32066

European-Finnish (FIN) AF: 0.470 AC: 8421 AN: 17902

Middle Eastern (MID) AF: 0.412 AC: 578 AN: 1402

European-Non Finnish (NFE) AF: 0.412 AC: 80885 AN: 196490

Other (OTH) AF: 0.419 AC: 7820 AN: 18666

GnomAD4 genome AF: 0.386 AC: 58727 AN: 152062 Hom.: 11565 Cov.: 32 AF XY: 0.385 AC XY: 28653 AN XY: 74334

African (AFR) AF: 0.325 AC: 13463 AN: 41476

American (AMR) AF: 0.340 AC: 5190 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2448 AN: 5172

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4826

European-Finnish (FIN) AF: 0.474 AC: 5007 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28145 AN: 67962

Other (OTH) AF: 0.407 AC: 860 AN: 2112

Alfa AF: 0.403 Hom.: 2002

Bravo AF: 0.378

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.22
DANN	Benign	0.46
PhyloP100		-1.7
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

Other links and lift over

dbSNP: rs8051405; hg19: chr16-56717596;