NM_130849.4:c.1114G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. V372V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.77 (54442 hom., cov: 33)
  • Exomes 𝑓: 0.97 (703395 hom.)
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• Publications: 41 publications found

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]

SLC39A4 Gene-Disease associations (from GenCC):

• acrodermatitis enteropathica

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen

LOC124902041 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007178992).
• BP6: Variant 8-144414297-C-G is Benign according to our data. Variant chr8-144414297-C-G is described in ClinVar as Benign. ClinVar VariationId is 3910723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130849.4. 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
	SLC39A4	NM_130849.4	MANE Select	c.1114G>C	p.Val372Leu	missense	Exon 6 of 12	NP_570901.3	Q6P5W5-1
	SLC39A4	NM_017767.3		c.1039G>C	p.Val347Leu	missense	Exon 5 of 11	NP_060237.3	Q6P5W5-2
	SLC39A4	NM_001374839.1		c.832G>C	p.Val278Leu	missense	Exon 5 of 11	NP_001361768.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A4	ENST00000301305.8	TSL:1 MANE Select	c.1114G>C	p.Val372Leu	missense	Exon 6 of 12	ENSP00000301305.4	Q6P5W5-1
	SLC39A4	ENST00000276833.9	TSL:2	c.1039G>C	p.Val347Leu	missense	Exon 5 of 11	ENSP00000276833.5	Q6P5W5-2
	SLC39A4	ENST00000531789.1	TSL:3	n.-216G>C		upstream_gene	N/A

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

African (AFR) AF: 0.176 AC: 5891 AN: 33426

American (AMR) AF: 0.953 AC: 41547 AN: 43606

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 25515 AN: 25818

East Asian (EAS) AF: 1.00 AC: 39438 AN: 39440

South Asian (SAS) AF: 0.998 AC: 84467 AN: 84604

European-Finnish (FIN) AF: 1.00 AC: 52548 AN: 52550

Middle Eastern (MID) AF: 0.949 AC: 5432 AN: 5726

European-Non Finnish (NFE) AF: 0.997 AC: 1107589 AN: 1110428

Other (OTH) AF: 0.944 AC: 56799 AN: 60158

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

African (AFR) AF: 0.205 AC: 8515 AN: 41450

American (AMR) AF: 0.907 AC: 13868 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 3428 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 0.997 AC: 4811 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67719 AN: 67972

Other (OTH) AF: 0.825 AC: 1744 AN: 2114

Alfa AF: 0.927 Hom.: 20274

Bravo AF: 0.735

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.033
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	13
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0072	T
PhyloP100		1.2
Sift4G	Benign	1.0	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

Other links and lift over

dbSNP: rs1871534; hg19: chr8-145639681;