8-144416001-G-T

Position:

• chr8-144416001-G-T

Variant summary

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

The NM_130849.4(SLC39A4):​c.283C>A​(p.Arg95Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A4	NM_130849.4	c.283C>A	p.Arg95Ser	missense_variant	2/12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8	c.283C>A	p.Arg95Ser	missense_variant	2/12	1	NM_130849.4	ENSP00000301305.4
SLC39A4	ENST00000276833.9	c.208C>A	p.Arg70Ser	missense_variant	1/11	2		ENSP00000276833.5
SLC39A4	ENST00000526658.1	c.193-582C>A		intron_variant		3		ENSP00000434512.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1430672 Hom.: 0 Cov.: 83 AF XY: 0.00 AC XY: 0 AN XY: 708246

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.80	.;P
Vest4		0.34
MutPred		0.61		.;Loss of methylation at R95 (P = 0.0464);
MVP		0.80
MPC		0.49
ClinPred		0.94	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs121434292; hg19: chr8-145641385;