Genetic Variant SLC6A12:p.Gln98Gln (chr12-204619-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001122848.3(SLC6A12):c.294A>G(p.Gln98Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,614,164 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 23 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 17 hom. )

Consequence

SLC6A12
NM_001122848.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

SLC6A12 (HGNC:11045): (solute carrier family 6 member 12) Enables monocarboxylic acid transmembrane transporter activity. Involved in monocarboxylic acid transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in neuron projection. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC6A12 links:

SLC6A12-AS1 (HGNC:40548): (SLC6A12 antisense RNA 1)

SLC6A12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006742269).

BP6

Variant 12-204619-T-C is Benign according to our data. Variant chr12-204619-T-C is described in ClinVar as [Benign]. Clinvar id is 781056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.56 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00901 (1372/152300) while in subpopulation AFR AF= 0.0312 (1296/41546). AF 95% confidence interval is 0.0298. There are 23 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A12	NM_001122848.3 link	c.294A>G	p.Gln98Gln	synonymous_variant	Exon 4 of 16	ENST00000684302.1	NP_001116320.1	P48065

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A12	ENST00000684302.1 link	c.294A>G	p.Gln98Gln	synonymous_variant	Exon 4 of 16		NM_001122848.3	ENSP00000508194.1		P48065

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

1362

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00238

AC:

599

AN:

251376

Hom.:

AF XY:

0.00155

AC XY:

211

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000884

AC:

1292

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000745

AC XY:

542

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0312

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000647

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00901

AC:

1372

AN:

152300

Hom.:

Cov.:

AF XY:

0.00859

AC XY:

640

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0312

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00533

Hom.:

Bravo

AF:

0.0103

ESP6500AA

AF:

0.0302

AC:

133

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00292

AC:

355

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Benign

2.7

DANN

Benign

0.57

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.95

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Benign

0.65

MVP

0.54

ClinPred

0.083

GERP RS

1.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over