rs1871534

Variant names:

• chr8-144414297-C-G
• rs1871534
• NM_130849.4:c.1114G>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM5 BP4_Strong BA1

The NM_130849.4(SLC39A4):​c.1114G>C​(p.Val372Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,607,874 control chromosomes in the GnomAD database, including 757,837 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V372P) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.77 (54442 hom., cov: 33)
  • Exomes 𝑓: 0.97 (703395 hom.)
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

Genes affected

SLC39A4 (HGNC:17129): (solute carrier family 39 member 4) This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. Mutations in this gene result in acrodermatitis enteropathica. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

LOC124902041 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
• BP4: Computational evidence support a benign effect (MetaRNN=0.007178992).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A4	NM_130849.4	c.1114G>C	p.Val372Leu	missense_variant	Exon 6 of 12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8	c.1114G>C	p.Val372Leu	missense_variant	Exon 6 of 12	1	NM_130849.4	ENSP00000301305.4
SLC39A4	ENST00000276833.9	c.1039G>C	p.Val347Leu	missense_variant	Exon 5 of 11	2		ENSP00000276833.5
SLC39A4	ENST00000531789.1	n.-216G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117029 AN: 152000 Hom.: 54429 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.975 AC: 1419226 AN: 1455756 Hom.: 703395 Cov.: 92 AF XY: 0.978 AC XY: 707764 AN XY: 723514

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.953

Gnomad4 ASJ exome AF: 0.988

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.998

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.944

GnomAD4 genome AF: 0.770 AC: 117059 AN: 152118 Hom.: 54442 Cov.: 33 AF XY: 0.778 AC XY: 57840 AN XY: 74372

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.987

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.825

Alfa AF: 0.927 Hom.: 20274

Bravo AF: 0.735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.033
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	13
LIST_S2	Benign	0.26	T;T
MetaRNN	Benign	0.0072	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1871534; hg19: chr8-145639681;