1-153966654-C-T

Position:

• chr1-153966654-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014437.5(SLC39A1):​c.-140+732G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,874 control chromosomes in the GnomAD database, including 26,792 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 0.58 (26788 hom., cov: 32)
  • Exomes 𝑓: 0.50 (4 hom.)
• Consequence: SLC39A1 NM_014437.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

SLC39A1 (HGNC:12876): (solute carrier family 39 member 1) This gene encodes a member of the zinc-iron permease family. The encoded protein is localized to the cell membrane and acts as a zinc uptake transporter. This gene has been linked to prostate cancer, breast cancer, and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ENSG00000285779 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A1	NM_001271960.2	c.-140+1430G>A		intron_variant			NP_001258889.1
SLC39A1	NM_014437.5	c.-140+732G>A		intron_variant			NP_055252.2
SLC39A1	XM_047418008.1	c.-242+732G>A		intron_variant			XP_047273964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285779	ENST00000648921.1	n.193-2951G>A		intron_variant				ENSP00000498105.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88074 AN: 151736 Hom.: 26738 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.500 AC: 10 AN: 20 Hom.: 4 Cov.: 0 AF XY: 0.357 AC XY: 5 AN XY: 14

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.563

GnomAD4 genome AF: 0.581 AC: 88179 AN: 151854 Hom.: 26788 Cov.: 32 AF XY: 0.589 AC XY: 43744 AN XY: 74208

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.555

Alfa AF: 0.501 Hom.: 18919

Bravo AF: 0.598

Asia WGS AF: 0.762 AC: 2648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11264736; hg19: chr1-153939130;