Genetic Variant NM_004696.3:c.1369G>T (chr1-110363861-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004696.3(SLC16A4):c.1369G>T(p.Gly457Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,512 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: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLC16A4
NM_004696.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14910296).

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.1369G>T	p.Gly457Cys	missense	Exon 9 of 9	NP_004687.1	O15374-1
SLC16A4	NM_001201546.2		c.1225G>T	p.Gly409Cys	missense	Exon 8 of 8	NP_001188475.1	O15374-5
SLC16A4	NM_001201547.2		c.1183G>T	p.Gly395Cys	missense	Exon 8 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.1369G>T	p.Gly457Cys	missense	Exon 9 of 9	ENSP00000358794.4	O15374-1
SLC16A4	ENST00000472422.6	TSL:1	c.1225G>T	p.Gly409Cys	missense	Exon 8 of 8	ENSP00000432495.1	O15374-5
SLC16A4	ENST00000369781.8	TSL:1	c.865G>T	p.Gly289Cys	missense	Exon 8 of 8	ENSP00000358796.4	O15374-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460512

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.00

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111470

Other (OTH)

AF:

0.00

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.014

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.84

M_CAP

Benign

0.0098

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.93

PhyloP100

1.9

PrimateAI

Benign

0.42

PROVEAN

Benign

1.9

REVEL

Benign

0.19

Sift

Benign

0.34

Sift4G

Benign

0.32

Polyphen

0.023

Vest4

0.24

MutPred

0.54

Gain of glycosylation at S462 (P = 0.136)

MVP

0.78

MPC

0.10

ClinPred

0.95

GERP RS

2.9

Varity_R

0.10

gMVP

0.58

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over