chr12-56235666-T-G

Position:

• chr12-56235666-T-G

Variant summary

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

The NM_173596.3(SLC39A5):​c.911T>G​(p.Met304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC39A5 NM_173596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

SLC39A5 (HGNC:20502): (solute carrier family 39 member 5) The protein encoded by this gene belongs to the ZIP family of zinc transporters that transport zinc into cells from outside, and play a crucial role in controlling intracellular zinc levels. Zinc is an essential cofactor for many enzymes and proteins involved in gene transcription, growth, development and differentiation. Mutations in this gene have been associated with autosomal dominant high myopia (MYP24). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

SLC39A5 (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
SLC39A5	NM_173596.3	c.911T>G	p.Met304Arg	missense_variant	8/13	ENST00000454355.7	NP_775867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A5	ENST00000454355.7	c.911T>G	p.Met304Arg	missense_variant	8/13	1	NM_173596.3	ENSP00000405360.2
SLC39A5	ENST00000266980.8	c.911T>G	p.Met304Arg	missense_variant	6/11	1		ENSP00000266980.4
SLC39A5	ENST00000481103.5	n.780T>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251270 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135804

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461790 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727196

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: 0.0000116

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	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.53	.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.29
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.11	B;B
Vest4		0.59
MutPred		0.78		Gain of methylation at M304 (P = 0.0123);Gain of methylation at M304 (P = 0.0123);
MVP		0.076
MPC		0.29
ClinPred		0.15	T
GERP RS		-4.1
Varity_R		0.92
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs587777625; hg19: chr12-56629450;