dbSNP rs35157487: SLC16A4:p.Ala185Thr (chr1-110379330-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004696.3(SLC16A4):c.553G>A(p.Ala185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,602,770 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 39 hom. )

Consequence

SLC16A4
NM_004696.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.30

Publications

8 publications found

Variant links:

Genes affected

SLC16A4 (HGNC:10925): (solute carrier family 16 member 4) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC16A4 links:

LAMTOR5-AS1 (HGNC:40823): (LAMTOR5 and SLC16A4 antisense RNA 1)

LAMTOR5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023040175).

BP6

Variant 1-110379330-C-T is Benign according to our data. Variant chr1-110379330-C-T is described in ClinVar as Benign. ClinVar VariationId is 769522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2177/152236) while in subpopulation AFR AF = 0.0498 (2067/41522). AF 95% confidence interval is 0.048. There are 50 homozygotes in GnomAd4. There are 1042 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004696.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A4	NM_004696.3	MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 6 of 9	NP_004687.1	O15374-1
SLC16A4	NM_001201546.2		c.409G>A	p.Ala137Thr	missense	Exon 5 of 8	NP_001188475.1	O15374-5
SLC16A4	NM_001201547.2		c.367G>A	p.Ala123Thr	missense	Exon 5 of 8	NP_001188476.1	O15374-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A4	ENST00000369779.9	TSL:1 MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 6 of 9	ENSP00000358794.4	O15374-1
SLC16A4	ENST00000472422.6	TSL:1	c.409G>A	p.Ala137Thr	missense	Exon 5 of 8	ENSP00000432495.1	O15374-5
SLC16A4	ENST00000369781.8	TSL:1	c.526+1652G>A		intron	N/A	ENSP00000358796.4	O15374-3

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2177

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.00372

AC:

927

AN:

249224

AF XY:

0.00282

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00157

AC:

2279

AN:

1450534

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1003

AN XY:

719260

show subpopulations

African (AFR)

AF:

0.0505

AC:

1678

AN:

33200

American (AMR)

AF:

0.00252

AC:

111

AN:

44128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25950

East Asian (EAS)

AF:

0.00

AC:

AN:

39366

South Asian (SAS)

AF:

0.000163

AC:

AN:

85826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00245

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.000247

AC:

272

AN:

1103210

Other (OTH)

AF:

0.00318

AC:

190

AN:

59816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

113

225

338

450

563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0143

AC:

2177

AN:

152236

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1042

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0498

AC:

2067

AN:

41522

American (AMR)

AF:

0.00438

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68014

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

103

206

310

413

516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00524

Hom.:

Bravo

AF:

0.0162

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0502

AC:

221

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00462

AC:

561

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

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

Benign

0.065

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.045

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.14

PhyloP100

1.3

PrimateAI

Benign

0.28

PROVEAN

Benign

0.010

REVEL

Benign

0.035

Sift

Benign

0.16

Sift4G

Benign

0.95

Polyphen

0.0010

Vest4

0.017

MVP

0.27

MPC

0.089

ClinPred

0.0028

GERP RS

-1.7

PromoterAI

-0.0068

Neutral

(source)

Varity_R

0.061

gMVP

0.34

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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