10-89433263-A-G

Variant names:

• chr10-89433263-A-G
• NM_213606.4:c.1352T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_213606.4(SLC16A12):​c.1352T>C​(p.Ile451Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A12 NM_213606.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.28
• Publications: 0 publications found

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]

SLC16A12-AS1 (HGNC:51205): (SLC16A12 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213606.4. 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
	SLC16A12	NM_213606.4	MANE Select	c.1352T>C	p.Ile451Thr	missense	Exon 8 of 8	NP_998771.3	Q6ZSM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A12	ENST00000371790.5	TSL:2 MANE Select	c.1352T>C	p.Ile451Thr	missense	Exon 8 of 8	ENSP00000360855.4	Q6ZSM3
	SLC16A12	ENST00000899673.1		c.1352T>C	p.Ile451Thr	missense	Exon 7 of 7	ENSP00000569732.1
	SLC16A12	ENST00000899674.1		c.1352T>C	p.Ile451Thr	missense	Exon 8 of 8	ENSP00000569733.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.29	D
PhyloP100		8.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.086	T
Vest4		0.64
MVP		0.87
MPC		0.64
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.33
gMVP		0.41
Mutation Taster		=52/48	polymorphism

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

hg19: chr10-91193020;