8-144414422-C-A

Variant names:

• chr8-144414422-C-A
• NM_130849.4:c.989G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_130849.4(SLC39A4):​c.989G>T​(p.Gly330Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,406,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A4	NM_130849.4	c.989G>T	p.Gly330Val	missense_variant	Exon 6 of 12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8	c.989G>T	p.Gly330Val	missense_variant	Exon 6 of 12	1	NM_130849.4	ENSP00000301305.4
SLC39A4	ENST00000276833.9	c.914G>T	p.Gly305Val	missense_variant	Exon 5 of 11	2		ENSP00000276833.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1406750 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 694456

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: 0.00000185

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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0050	D;T
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	.;D
Vest4		0.58
MutPred		0.74		.;Loss of disorder (P = 0.0926);
MVP		0.74
MPC		0.64
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.63
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145639806;