chr2-230046295-C-T

Variant summary

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

The NM_152527.5(SLC16A14):​c.831G>A​(p.Met277Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SLC16A14
NM_152527.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.541
Variant links:
Genes affected
SLC16A14 (HGNC:26417): (solute carrier family 16 member 14) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. 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=0.08835411).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC16A14NM_152527.5 linkc.831G>A p.Met277Ile missense_variant Exon 4 of 5 ENST00000295190.9 NP_689740.2 Q7RTX9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC16A14ENST00000295190.9 linkc.831G>A p.Met277Ile missense_variant Exon 4 of 5 1 NM_152527.5 ENSP00000295190.4 Q7RTX9-1
SLC16A14ENST00000457406.5 linkc.831G>A p.Met277Ile missense_variant Exon 4 of 4 1 ENSP00000400352.1 E7EMG7
SLC16A14ENST00000412034.5 linkc.831G>A p.Met277Ile missense_variant Exon 5 of 5 2 ENSP00000395775.1 Q6ZWE5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1461870
Hom.:
0
Cov.:
32
AF XY:
0.0000413
AC XY:
30
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.831G>A (p.M277I) alteration is located in exon 4 (coding exon 3) of the SLC16A14 gene. This alteration results from a G to A substitution at nucleotide position 831, causing the methionine (M) at amino acid position 277 to be replaced by an isoleucine (I). 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
0.12
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
5.8
DANN
Benign
0.63
DEOGEN2
Benign
0.13
T;.;.
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.59
T;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.088
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.2
L;.;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.52
N;N;N
REVEL
Benign
0.096
Sift
Benign
0.46
T;T;T
Sift4G
Benign
0.59
T;.;.
Polyphen
0.0
B;B;.
Vest4
0.15
MutPred
0.54
Loss of catalytic residue at M277 (P = 7e-04);Loss of catalytic residue at M277 (P = 7e-04);Loss of catalytic residue at M277 (P = 7e-04);
MVP
0.12
MPC
0.41
ClinPred
0.11
T
GERP RS
1.9
Varity_R
0.071
gMVP
0.45

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: rs377600815; hg19: chr2-230911011; API