Genetic Variant SLC16A14:p.Thr356Met (chr2-230046059-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152527.5(SLC16A14):c.1067C>T(p.Thr356Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC16A14
NM_152527.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

Publications

0 publications found

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]

SLC16A14 links:

LOC107985996 (HGNC:):

LOC107985996 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3912204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A14	NM_152527.5 link	c.1067C>T	p.Thr356Met	missense_variant	Exon 4 of 5	ENST00000295190.9	NP_689740.2	Q7RTX9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A14	ENST00000295190.9 link	c.1067C>T	p.Thr356Met	missense_variant	Exon 4 of 5	1	NM_152527.5	ENSP00000295190.4	Q7RTX9-1
SLC16A14	ENST00000457406.5 link	c.1067C>T	p.Thr356Met	missense_variant	Exon 4 of 4	1		ENSP00000400352.1	E7EMG7
SLC16A14	ENST00000412034.5 link	c.1067C>T	p.Thr356Met	missense_variant	Exon 5 of 5	2		ENSP00000395775.1	Q6ZWE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 04, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1067C>T (p.T356M) alteration is located in exon 4 (coding exon 3) of the SLC16A14 gene. This alteration results from a C to T substitution at nucleotide position 1067, causing the threonine (T) at amino acid position 356 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

0.26

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.0

L;.;.

PhyloP100

4.6

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.75

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.068

T;T;T

Sift4G

Benign

0.20

T;.;.

Polyphen

1.0

D;D;.

Vest4

0.76

MutPred

0.55

Gain of catalytic residue at V352 (P = 0.0748);Gain of catalytic residue at V352 (P = 0.0748);Gain of catalytic residue at V352 (P = 0.0748);

MVP

0.68

MPC

1.2

ClinPred

0.92

GERP RS

4.9

Varity_R

0.083

gMVP

0.82

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over