Genetic Variant NM_004207.4:c.44C>T (chr17-82236052-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2

The NM_004207.4(SLC16A3):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,612,684 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 58 hom. )

Consequence

SLC16A3
NM_004207.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.84

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.225).

BP6

Variant 17-82236052-C-T is Benign according to our data. Variant chr17-82236052-C-T is described in ClinVar as Benign. ClinVar VariationId is 725993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00253 (385/152356) while in subpopulation SAS AF = 0.0325 (157/4832). AF 95% confidence interval is 0.0283. There are 3 homozygotes in GnomAd4. There are 232 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004207.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A3	NM_004207.4	MANE Select	c.44C>T	p.Ala15Val	missense	Exon 2 of 5	NP_004198.1	O15427
SLC16A3	NM_001042422.3		c.44C>T	p.Ala15Val	missense	Exon 2 of 5	NP_001035887.1	O15427
SLC16A3	NM_001042423.3		c.44C>T	p.Ala15Val	missense	Exon 2 of 5	NP_001035888.1	O15427

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A3	ENST00000582743.6	TSL:1 MANE Select	c.44C>T	p.Ala15Val	missense	Exon 2 of 5	ENSP00000462405.1	O15427
SLC16A3	ENST00000581287.5	TSL:1	c.44C>T	p.Ala15Val	missense	Exon 1 of 4	ENSP00000463978.1	O15427
SLC16A3	ENST00000392339.6	TSL:5	c.44C>T	p.Ala15Val	missense	Exon 2 of 5	ENSP00000376150.1	O15427

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.0327

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00442

AC:

1101

AN:

248934

AF XY:

0.00544

show subpopulations

Gnomad AFR exome

AF:

0.00393

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00747

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000420

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00237

AC:

3461

AN:

1460328

Hom.:

Cov.:

AF XY:

0.00315

AC XY:

2291

AN XY:

726458

show subpopulations

African (AFR)

AF:

0.00448

AC:

150

AN:

33474

American (AMR)

AF:

0.000380

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

26130

East Asian (EAS)

AF:

0.0124

AC:

491

AN:

39696

South Asian (SAS)

AF:

0.0265

AC:

2289

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52158

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000201

AC:

223

AN:

1111794

Other (OTH)

AF:

0.00351

AC:

212

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

248

496

745

993

1241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00253

AC:

385

AN:

152356

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

232

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00322

AC:

134

AN:

41580

American (AMR)

AF:

0.000196

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.0112

AC:

AN:

5184

South Asian (SAS)

AF:

0.0325

AC:

157

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00199

Hom.:

Bravo

AF:

0.00186

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00505

AC:

612

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

PhyloP100

7.8

ClinPred

0.024

GERP RS

5.3

PromoterAI

-0.082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over