10-89436227-G-T

Position:

• chr10-89436227-G-T

Variant summary

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

The NM_213606.4(SLC16A12):​c.1121C>A​(p.Pro374His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A12 NM_213606.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.71

Genes affected

SLC16A12 (HGNC:23094): (solute carrier family 16 member 12) This gene encodes a transmembrane transporter that likely plays a role in monocarboxylic acid transport. A mutation in this gene has been associated with juvenile cataracts with microcornea and renal glucosuria. [provided by RefSeq, Mar 2010]

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
SLC16A12	NM_213606.4	c.1121C>A	p.Pro374His	missense_variant	7/8	ENST00000371790.5	NP_998771.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A12	ENST00000371790.5	c.1121C>A	p.Pro374His	missense_variant	7/8	2	NM_213606.4	ENSP00000360855	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC16A12-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 15, 2024

The SLC16A12 c.1121C>A variant is predicted to result in the amino acid substitution p.Pro374His. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.16	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.046	D
Vest4		0.56
MVP		0.89
MPC		0.69
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-91195984;