17-82237416-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004207.4(SLC16A3):c.646C>T(p.Arg216Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,570,726 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R216L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SLC16A3
NM_004207.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

Publications

0 publications found

Variant links:

Genes affected

SLC16A3 (HGNC:10924): (solute carrier family 16 member 3) Lactic acid and pyruvate transport across plasma membranes is catalyzed by members of the proton-linked monocarboxylate transporter (MCT) family, which has been designated solute carrier family-16. Each MCT appears to have slightly different substrate and inhibitor specificities and transport kinetics, which are related to the metabolic requirements of the tissues in which it is found. The MCTs, which include MCT1 (SLC16A1; MIM 600682) and MCT2 (SLC16A7; MIM 603654), are characterized by 12 predicted transmembrane domains (Price et al., 1998 [PubMed 9425115]).[supplied by OMIM, Mar 2008]

SLC16A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2081053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A3	NM_004207.4 link	c.646C>T	p.Arg216Cys	missense_variant	Exon 4 of 5	ENST00000582743.6	NP_004198.1	O15427A0A024R8U1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A3	ENST00000582743.6 link	c.646C>T	p.Arg216Cys	missense_variant	Exon 4 of 5	1	NM_004207.4	ENSP00000462405.1		O15427

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000160

AC:

AN:

181312

AF XY:

0.000221

show subpopulations

Gnomad AFR exome

AF:

0.0000989

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000114

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000728

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000150

AC:

213

AN:

1418526

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

123

AN XY:

702420

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32638

American (AMR)

AF:

0.00

AC:

AN:

39416

Ashkenazi Jewish (ASJ)

AF:

0.0000394

AC:

AN:

25402

East Asian (EAS)

AF:

0.00

AC:

AN:

37614

South Asian (SAS)

AF:

0.000580

AC:

AN:

82786

European-Finnish (FIN)

AF:

0.0000219

AC:

AN:

45586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.000142

AC:

155

AN:

1090782

Other (OTH)

AF:

0.000119

AC:

AN:

58634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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

AF:

0.0000920

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000537

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000849

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.646C>T (p.R216C) alteration is located in exon 4 (coding exon 3) of the SLC16A3 gene. This alteration results from a C to T substitution at nucleotide position 646, causing the arginine (R) at amino acid position 216 to be replaced by a cysteine (C). 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

0.24

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Uncertain

0.45

.;T;.;T;T;.;T;T;T;.;T;T

Eigen

Benign

-0.024

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

D;D;D;.;D;D;.;.;.;D;.;D

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

.;L;.;L;.;.;L;L;L;.;L;.

PhyloP100

3.2

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.6

.;D;.;.;.;.;D;.;.;.;.;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

.;D;.;.;.;.;D;.;.;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.99

.;D;.;D;.;.;D;D;D;.;D;.

Vest4

0.59, 0.60, 0.59, 0.65

MutPred

0.63

Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);.;Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);Loss of disorder (P = 0.0141);.;

MVP

0.68

MPC

0.98

ClinPred

0.16

GERP RS

1.5

PromoterAI

-0.0054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.59

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over