rs8051405

chr16-56683684-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MT1X	NM_005952.4	c.95-274G>A		intron_variant		ENST00000394485.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1X	ENST00000394485.5	c.95-274G>A		intron_variant		1	NM_005952.4	P1
MT1X	ENST00000564974.1	c.*110-274G>A		intron_variant, NMD_transcript_variant		1
MT1X	ENST00000568370.1	n.1215G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.419

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

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.407

Alfa AF: 0.405 Hom.: 1960

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs8051405; hg19: chr16-56717596;