NM_213606.4:c.1441A>C

Variant names:

• chr10-89433174-T-G
• rs1004436880
• NM_213606.4:c.1441A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict 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
• 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 0 ACMG points.

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

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.1441A>C	p.Lys481Gln	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.1441A>C	p.Lys481Gln	missense	Exon 8 of 8	ENSP00000360855.4	Q6ZSM3
	SLC16A12	ENST00000899673.1		c.1441A>C	p.Lys481Gln	missense	Exon 7 of 7	ENSP00000569732.1
	SLC16A12	ENST00000899674.1		c.1441A>C	p.Lys481Gln	missense	Exon 8 of 8	ENSP00000569733.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.5
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
Mutation Taster		=92/8	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

dbSNP: rs1004436880; hg19: chr10-91192931;