Genetic Variant SLC29A4:p.Ala36Val (chr7-5287923-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153247.4(SLC29A4):c.107C>T(p.Ala36Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000714 in 1,611,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

SLC29A4
NM_153247.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.129

Variant links:

Genes affected

SLC29A4 (HGNC:23097): (solute carrier family 29 member 4) This gene encodes a member of the SLC29A/ENT transporter protein family. The encoded membrane protein catalyzes the reuptake of monoamines into presynaptic neurons, thus determining the intensity and duration of monoamine neural signaling. It has been shown to transport several compounds, including serotonin, dopamine, and the neurotoxin 1-methyl-4-phenylpyridinium. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

SLC29A4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017153114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A4	NM_153247.4 link	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 11	ENST00000396872.8	NP_694979.2	Q7RTT9-1
SLC29A4	NM_001040661.3 link	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 11		NP_001035751.1	Q7RTT9-1
SLC29A4	NM_001300847.3 link	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 11		NP_001287776.1	Q7RTT9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A4	ENST00000396872.8 link	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 11	1	NM_153247.4	ENSP00000380081.2		Q7RTT9-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000971

AC:

AN:

247202

Hom.:

AF XY:

0.0000818

AC XY:

AN XY:

134508

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1459416

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726028

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000929

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000309

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107C>T (p.A36V) alteration is located in exon 2 (coding exon 1) of the SLC29A4 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the alanine (A) at amino acid position 36 to be replaced by a valine (V). 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

0.078

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.20

DANN

Benign

0.95

DEOGEN2

Benign

0.043

.;T;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.40

T;.;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

.;L;.;L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.94

N;N;N;N;N

REVEL

Benign

0.0060

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T

Polyphen

0.0010, 0.0

.;B;.;B;B

Vest4

0.15, 0.17, 0.12

MVP

0.13

ClinPred

0.0049

GERP RS

-2.4

Varity_R

0.020

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over