rs587777625

Positions:

• chr12-56235666-T-C
• chr12-56235666-T-G

Variant summary

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

The NM_173596.3(SLC39A5):​c.911T>C​(p.Met304Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A5 NM_173596.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-56235666-T-C is Pathogenic according to our data. Variant chr12-56235666-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 143992.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A5	NM_173596.3	c.911T>C	p.Met304Thr	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>C	p.Met304Thr	missense_variant	8/13	1	NM_173596.3	ENSP00000405360	P1
SLC39A5	ENST00000266980.8	c.911T>C	p.Met304Thr	missense_variant	6/11	1		ENSP00000266980	P1
SLC39A5	ENST00000481103.5	n.780T>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Myopia 24, autosomal dominant Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.9
DANN	Benign	0.75
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.33	.;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N;N
REVEL	Pathogenic	0.69
Sift	Benign	0.30	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.0	B;B
Vest4		0.66
MutPred		0.70		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.061
MPC		0.13
ClinPred		0.23	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs587777625; hg19: chr12-56629450;