rs2130791552

Variant names:

• chr8-144412598-C-A
• rs2130791552
• NM_130849.4:c.1884G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144412598-C-A
• chr8-144412598-C-G
• chr8-144412598-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_130849.4(SLC39A4):​c.1884G>T​(p.Leu628Leu) 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L628L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A4 NM_130849.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700
• Publications: 0 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

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=-0.36).
• BP6: Variant 8-144412598-C-A is Benign according to our data. Variant chr8-144412598-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1125461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.007 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.1884G>T	p.Leu628Leu	synonymous	Exon 12 of 12	NP_570901.3	Q6P5W5-1
	SLC39A4	NM_017767.3		c.1809G>T	p.Leu603Leu	synonymous	Exon 11 of 11	NP_060237.3	Q6P5W5-2
	SLC39A4	NM_001374839.1		c.1602G>T	p.Leu534Leu	synonymous	Exon 11 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.1884G>T	p.Leu628Leu	synonymous	Exon 12 of 12	ENSP00000301305.4	Q6P5W5-1
	SLC39A4	ENST00000532718.5	TSL:1	n.484G>T		non_coding_transcript_exon	Exon 4 of 4
	SLC39A4	ENST00000276833.9	TSL:2	c.1809G>T	p.Leu603Leu	synonymous	Exon 11 of 11	ENSP00000276833.5	Q6P5W5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	6.8
DANN	Benign	0.89
PhyloP100		-0.0070

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: rs2130791552; hg19: chr8-145637982;