rs3740030

Variant names:

• chr10-89462530-A-C
• rs3740030
• NM_213606.4:c.49T>G
• SLC16A12 p.Trp17Gly

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213606.4(SLC16A12):​c.49T>G​(p.Trp17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,613,154 control chromosomes in the GnomAD database, including 6,627 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (491 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6136 hom.)
• Consequence: SLC16A12 NM_213606.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.31
• Publications: 18 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035749376).
• BP6: Variant 10-89462530-A-C is Benign according to our data. Variant chr10-89462530-A-C is described in ClinVar as Benign. ClinVar VariationId is 681342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

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.49T>G	p.Trp17Gly	missense	Exon 3 of 8	NP_998771.3	Q6ZSM3
	SLC16A12-AS1	NR_120614.1		n.274A>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A12	ENST00000371790.5	TSL:2 MANE Select	c.49T>G	p.Trp17Gly	missense	Exon 3 of 8	ENSP00000360855.4	Q6ZSM3
	SLC16A12	ENST00000899673.1		c.49T>G	p.Trp17Gly	missense	Exon 2 of 7	ENSP00000569732.1
	SLC16A12	ENST00000899674.1		c.49T>G	p.Trp17Gly	missense	Exon 3 of 8	ENSP00000569733.1

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10247 AN: 152030 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.0637

GnomAD2 exomes AF: 0.0796 AC: 19814 AN: 249050 AF XY: 0.0786

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.0306

Gnomad ASJ exome AF: 0.0619

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0929

Gnomad OTH exome AF: 0.0738

GnomAD4 exome AF: 0.0859 AC: 125507 AN: 1461004 Hom.: 6136 Cov.: 31 AF XY: 0.0843 AC XY: 61251 AN XY: 726826

African (AFR) AF: 0.0122 AC: 407 AN: 33458

American (AMR) AF: 0.0320 AC: 1429 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 1605 AN: 26134

East Asian (EAS) AF: 0.190 AC: 7530 AN: 39646

South Asian (SAS) AF: 0.0265 AC: 2281 AN: 86238

European-Finnish (FIN) AF: 0.112 AC: 5935 AN: 52962

Middle Eastern (MID) AF: 0.0187 AC: 108 AN: 5766

European-Non Finnish (NFE) AF: 0.0910 AC: 101194 AN: 1111778

Other (OTH) AF: 0.0832 AC: 5018 AN: 60348

GnomAD4 genome AF: 0.0673 AC: 10238 AN: 152150 Hom.: 491 Cov.: 32 AF XY: 0.0679 AC XY: 5049 AN XY: 74366

African (AFR) AF: 0.0161 AC: 667 AN: 41530

American (AMR) AF: 0.0425 AC: 649 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1070 AN: 5156

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0899 AC: 6113 AN: 67980

Other (OTH) AF: 0.0626 AC: 132 AN: 2110

Alfa AF: 0.0801 Hom.: 1906

Bravo AF: 0.0608

Asia WGS AF: 0.100 AC: 347 AN: 3478

EpiCase AF: 0.0809

EpiControl AF: 0.0808

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.76
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.040
Sift	Benign	0.46	T
Varity_R		0.40
gMVP		0.47
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3740030;

hg19: chr10-91222287;

COSMIC: COSV57947271;

COSMIC: COSV57947271;