rs3740030

Positions:

• chr10-89462530-A-C

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A12	NM_213606.4	c.49T>G	p.Trp17Gly	missense_variant	3/8	ENST00000371790.5
SLC16A12-AS1	NR_120614.1	n.274A>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A12	ENST00000371790.5	c.49T>G	p.Trp17Gly	missense_variant	3/8	2	NM_213606.4	P1
SLC16A12-AS1	ENST00000454270.5	n.201A>C		non_coding_transcript_exon_variant	2/3	2
SLC16A12	ENST00000475682.1	c.49T>G	p.Trp17Gly	missense_variant	3/3	3

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

GnomAD3 exomes AF: 0.0796 AC: 19814 AN: 249050 Hom.: 1109 AF XY: 0.0786 AC XY: 10601 AN XY: 134790

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 SAS exome AF: 0.0244

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

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.0614

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0910

Gnomad4 OTH exome AF: 0.0832

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

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0846 Hom.: 1284

Bravo AF: 0.0608

TwinsUK AF: 0.0928 AC: 344

ALSPAC AF: 0.0944 AC: 364

ESP6500AA AF: 0.0220 AC: 97

ESP6500EA AF: 0.0850 AC: 731

ExAC AF: 0.0794 AC: 9635

Asia WGS AF: 0.100 AC: 347 AN: 3478

EpiCase AF: 0.0809

EpiControl AF: 0.0808

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.040	N;D
REVEL	Benign	0.040
Sift	Benign	0.46	T;.
Vest4		0.033
MPC		0.28
ClinPred		0.0023	T
GERP RS		0.62
Varity_R		0.40
gMVP		0.47

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: rs3740030; hg19: chr10-91222287; COSMIC: COSV57947271; COSMIC: COSV57947271;