12-197458-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001122848.3(SLC6A12):​c.994G>A​(p.Val332Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLC6A12
NM_001122848.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.208707).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC6A12NM_001122848.3 linkuse as main transcriptc.994G>A p.Val332Met missense_variant 10/16 ENST00000684302.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC6A12ENST00000684302.1 linkuse as main transcriptc.994G>A p.Val332Met missense_variant 10/16 NM_001122848.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251084
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461700
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 12, 2021The c.994G>A (p.V332M) alteration is located in exon 11 (coding exon 8) of the SLC6A12 gene. This alteration results from a G to A substitution at nucleotide position 994, causing the valine (V) at amino acid position 332 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.067
T;T;T;T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.83
T;.;.;.
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Uncertain
2.2
M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.084
T;T;T;T
Sift4G
Uncertain
0.060
T;T;T;T
Polyphen
0.69
P;P;P;P
Vest4
0.23
MutPred
0.38
Loss of catalytic residue at V332 (P = 0.0407);Loss of catalytic residue at V332 (P = 0.0407);Loss of catalytic residue at V332 (P = 0.0407);Loss of catalytic residue at V332 (P = 0.0407);
MVP
0.56
ClinPred
0.18
T
GERP RS
2.5
Varity_R
0.044
gMVP
0.14

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.

Other links and lift over

dbSNP: rs747692783; hg19: chr12-306624; API