8-144415027-G-C

Variant names:

• chr8-144415027-G-C
• rs2977838
• NM_130849.4:c.751C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130849.4(SLC39A4):​c.751C>G​(p.Arg251Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09953153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A4	NM_130849.4	c.751C>G	p.Arg251Gly	missense_variant	Exon 4 of 12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8	c.751C>G	p.Arg251Gly	missense_variant	Exon 4 of 12	1	NM_130849.4	ENSP00000301305.4
SLC39A4	ENST00000276833.9	c.676C>G	p.Arg226Gly	missense_variant	Exon 3 of 11	2		ENSP00000276833.5
SLC39A4	ENST00000526658.1	c.469C>G	p.Arg157Gly	missense_variant	Exon 3 of 4	3		ENSP00000434512.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DEOGEN2	Benign	0.043	.;T;.
LIST_S2	Benign	0.27	T;T;T
MetaRNN	Benign	0.10	T;T;T
Sift4G	Uncertain	0.042	D;T;.
Vest4		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2977838; hg19: chr8-145640411;