rs121434290

chr8-144415966-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_130849.4(SLC39A4):c.318C>A(p.Asn106Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. N106N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.220

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-144415966-G-T is Pathogenic according to our data. Variant chr8-144415966-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 3540.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A4	NM_130849.4	c.318C>A	p.Asn106Lys	missense_variant	2/12	ENST00000301305.8
LOC124902041	XR_007061145.1	n.1435G>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A4	ENST00000301305.8	c.318C>A	p.Asn106Lys	missense_variant	2/12	1	NM_130849.4	P1
SLC39A4	ENST00000276833.9	c.243C>A	p.Asn81Lys	missense_variant	1/11	2
SLC39A4	ENST00000526658.1	c.193-547C>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443116 Hom.: 0 Cov.: 83 AF XY: 0.00 AC XY: 0 AN XY: 716466

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary acrodermatitis enteropathica Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	20
Dann	Uncertain	0.99
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	2.1e-7	A;A
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.083
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.42	.;B
Vest4		0.084
MutPred		0.41		.;Gain of ubiquitination at N106 (P = 0.0192);
MVP		0.53
MPC		0.25
ClinPred		0.28	T
GERP RS		2.6
Varity_R		0.062
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs121434290; hg19: chr8-145641350;