8-144412583-G-A

Variant names:

• chr8-144412583-G-A
• rs782025085
• NM_130849.4:c.1899C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_130849.4(SLC39A4):​c.1899C>T​(p.Thr633Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T633T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC39A4 NM_130849.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33
• 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: Orphanet, PanelApp Australia, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 8-144412583-G-A is Benign according to our data. Variant chr8-144412583-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1585825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.33 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.1899C>T	p.Thr633Thr	synonymous	Exon 12 of 12	NP_570901.3	Q6P5W5-1
	SLC39A4	NM_017767.3		c.1824C>T	p.Thr608Thr	synonymous	Exon 11 of 11	NP_060237.3	Q6P5W5-2
	SLC39A4	NM_001374839.1		c.1617C>T	p.Thr539Thr	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.1899C>T	p.Thr633Thr	synonymous	Exon 12 of 12	ENSP00000301305.4	Q6P5W5-1
	SLC39A4	ENST00000532718.5	TSL:1	n.499C>T		non_coding_transcript_exon	Exon 4 of 4
	SLC39A4	ENST00000276833.9	TSL:2	c.1824C>T	p.Thr608Thr	synonymous	Exon 11 of 11	ENSP00000276833.5	Q6P5W5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251352 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

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	-0.48
CADD	Benign	9.3
DANN	Benign	0.88
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs782025085; hg19: chr8-145637967;