rs587777625

Variant names:

• chr12-56235666-T-C
• rs587777625
• NM_173596.3:c.911T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• myopia 24, autosomal dominant

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 143992.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A5	NM_173596.3	c.911T>C	p.Met304Thr	missense_variant	Exon 8 of 13	ENST00000454355.7	NP_775867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A5	ENST00000454355.7	c.911T>C	p.Met304Thr	missense_variant	Exon 8 of 13	1	NM_173596.3	ENSP00000405360.2
SLC39A5	ENST00000266980.8	c.911T>C	p.Met304Thr	missense_variant	Exon 6 of 11	1		ENSP00000266980.4
SLC39A5	ENST00000481103.5	n.780T>C		non_coding_transcript_exon_variant	Exon 6 of 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

Aug 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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
PhyloP100		-0.037
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
Mutation Taster		=34/66	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs587777625; hg19: chr12-56629450;