Genetic Variant SLC29A4:p.Asp29Gly (chr7-5287902-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_153247.4(SLC29A4):c.86A>G(p.Asp29Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00277 in 1,612,106 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D29N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

SLC29A4
NM_153247.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.88

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007852465).

BP6

Variant 7-5287902-A-G is Benign according to our data. Variant chr7-5287902-A-G is described in ClinVar as [Benign]. Clinvar id is 3044053.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A4	NM_153247.4 link	c.86A>G	p.Asp29Gly	missense_variant	Exon 2 of 11	ENST00000396872.8	NP_694979.2	Q7RTT9-1
SLC29A4	NM_001040661.3 link	c.86A>G	p.Asp29Gly	missense_variant	Exon 2 of 11		NP_001035751.1	Q7RTT9-1
SLC29A4	NM_001300847.3 link	c.86A>G	p.Asp29Gly	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.86A>G	p.Asp29Gly	missense_variant	Exon 2 of 11	1	NM_153247.4	ENSP00000380081.2		Q7RTT9-1

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

361

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00245

AC:

609

AN:

248964

Hom.:

AF XY:

0.00236

AC XY:

319

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.000752

Gnomad AMR exome

AF:

0.00328

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00281

AC:

4099

AN:

1459740

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1978

AN XY:

726206

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000756

Gnomad4 NFE exome

AF:

0.00298

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00237

AC:

361

AN:

152366

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00257

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00171

AC:

207

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC29A4-related disorder

Benign:1

Feb 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

.;T;T;T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;.;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.0079

T;T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

.;M;.;M;M

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.89

N;N;N;N;N

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0080

D;D;D;D;D

Sift4G

Uncertain

0.044

D;D;D;D;D

Polyphen

0.78, 0.95

.;P;.;P;P

Vest4

0.65, 0.66, 0.57

MVP

0.76

ClinPred

0.031

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.12

gMVP

0.72

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

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