8-144415027-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_130849.4(SLC39A4):​c.751C>A​(p.Arg251Arg) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 23 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: Orphanet, PanelApp Australia, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

LOC124902041 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.318 with no splicing effect.

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.751C>A	p.Arg251Arg	synonymous	Exon 4 of 12	NP_570901.3
	SLC39A4	NM_017767.3		c.676C>A	p.Arg226Arg	synonymous	Exon 3 of 11	NP_060237.3
	SLC39A4	NM_001374839.1		c.469C>A	p.Arg157Arg	synonymous	Exon 3 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.751C>A	p.Arg251Arg	synonymous	Exon 4 of 12	ENSP00000301305.4
	SLC39A4	ENST00000276833.9	TSL:2	c.676C>A	p.Arg226Arg	synonymous	Exon 3 of 11	ENSP00000276833.5
	SLC39A4	ENST00000526658.1	TSL:3	c.469C>A	p.Arg157Arg	synonymous	Exon 3 of 4	ENSP00000434512.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2977838; hg19: chr8-145640411;