10-17961724-G-C

Variant names:

• chr10-17961724-G-C
• rs1834694698
• NM_001145195.2:c.405G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001282734.2(SLC39A12):​c.3G>C​(p.Met1?) variant causes a start lost 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A12 NM_001282734.2 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 49 codons. Genomic position: 17965486. Lost 0.087 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282734.2. 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.405G>C	p.Met135Ile	missense	Exon 3 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282734.2		c.3G>C	p.Met1?	start_lost	Exon 2 of 12	NP_001269663.1	Q504Y0-5
	SLC39A12	NM_001282733.2		c.405G>C	p.Met135Ile	missense	Exon 3 of 13	NP_001269662.1	Q504Y0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A12	ENST00000377369.7	TSL:1 MANE Select	c.405G>C	p.Met135Ile	missense	Exon 3 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.405G>C	p.Met135Ile	missense	Exon 3 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000539911.5	TSL:2	c.3G>C	p.Met1?	start_lost	Exon 2 of 12	ENSP00000440445.1	Q504Y0-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0043	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.039
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.051	T
Polyphen		0.32	B
Vest4		0.46
MutPred		0.25		Loss of ubiquitination at K132 (P = 0.0532)
MVP		0.21
MPC		0.027
ClinPred		0.62	D
GERP RS		4.4
Varity_R		0.22
gMVP		0.27
Mutation Taster		=36/164	disease causing

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: rs1834694698; hg19: chr10-18250653; COSMIC: COSV108222228;