chr10-89433174-T-G

Position:

• chr10-89433174-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_213606.4(SLC16A12):​c.1441A>C​(p.Lys481Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC16A12 NM_213606.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19597682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A12	NM_213606.4	c.1441A>C	p.Lys481Gln	missense_variant	8/8	ENST00000371790.5	NP_998771.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A12	ENST00000371790.5	c.1441A>C	p.Lys481Gln	missense_variant	8/8	2	NM_213606.4	ENSP00000360855.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 03, 2023

This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 481 of the SLC16A12 protein (p.Lys481Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC16A12-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	-0.060
Eigen_PC	Benign	0.084
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.078
Sift	Uncertain	0.023	D
Sift4G	Benign	0.095	T
Vest4		0.33
MVP		0.20
MPC		0.65
ClinPred		0.94	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.49

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: rs1004436880; hg19: chr10-91192931;