10-17978060-G-C

Variant names:

• chr10-17978060-G-C
• rs2478568
• NM_001145195.2:c.910G>C
• SLC39A12 p.Val304Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145195.2(SLC39A12):​c.910G>C​(p.Val304Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 26 publications found

Genes affected

SLC39A12 (HGNC:20860): (solute carrier family 39 member 12) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A12 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Aug 2008]

SLC39A12 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036914498).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A12	NM_001145195.2	MANE Select	c.910G>C	p.Val304Leu	missense	Exon 5 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.910G>C	p.Val304Leu	missense	Exon 5 of 13	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.910G>C	p.Val304Leu	missense	Exon 5 of 12	NP_689938.2	Q504Y0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A12	ENST00000377369.7	TSL:1 MANE Select	c.910G>C	p.Val304Leu	missense	Exon 5 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.910G>C	p.Val304Leu	missense	Exon 5 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.910G>C	p.Val304Leu	missense	Exon 5 of 12	ENSP00000366591.4	Q504Y0-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0010
DANN	Benign	0.26
DEOGEN2	Benign	0.00023	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.096	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		-3.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.059
Sift	Benign	0.30	T
Sift4G	Benign	0.75	T
Varity_R		0.050
gMVP		0.17
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2478568;

hg19: chr10-18266989;