rs17855765

Variant names:

• chr8-144415944-C-A
• NM_130849.4:c.340G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144415944-C-A
• chr8-144415944-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130849.4(SLC39A4):​c.340G>T​(p.Ala114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A114T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05485931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A4	NM_130849.4	c.340G>T	p.Ala114Ser	missense_variant	Exon 2 of 12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8	c.340G>T	p.Ala114Ser	missense_variant	Exon 2 of 12	1	NM_130849.4	ENSP00000301305.4
SLC39A4	ENST00000276833.9	c.265G>T	p.Ala89Ser	missense_variant	Exon 1 of 11	2		ENSP00000276833.5
SLC39A4	ENST00000526658.1	c.193-525G>T		intron_variant	Intron 1 of 3	3		ENSP00000434512.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440326 Hom.: 0 Cov.: 87 AF XY: 0.00000140 AC XY: 1 AN XY: 714894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.3
DANN	Benign	0.90
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.046
Sift	Benign	0.88	T;T
Sift4G	Uncertain	0.047	D;D
Polyphen		0.41	.;B
Vest4		0.047
MutPred		0.31		.;Gain of glycosylation at A114 (P = 0.0317);
MVP		0.23
MPC		0.35
ClinPred		0.088	T
GERP RS		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145641328;