Genetic Variant NM_153247.4:c.86A>T (chr7-5287902-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153247.4(SLC29A4):c.86A>T(p.Asp29Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D29G) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC29A4
NM_153247.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.88

Publications

6 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC29A4	NM_153247.4	MANE Select	c.86A>T	p.Asp29Val	missense	Exon 2 of 11	NP_694979.2	Q7RTT9-1
SLC29A4	NM_001040661.3		c.86A>T	p.Asp29Val	missense	Exon 2 of 11	NP_001035751.1	Q7RTT9-1
SLC29A4	NM_001300847.3		c.86A>T	p.Asp29Val	missense	Exon 2 of 11	NP_001287776.1	Q7RTT9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC29A4	ENST00000396872.8	TSL:1 MANE Select	c.86A>T	p.Asp29Val	missense	Exon 2 of 11	ENSP00000380081.2	Q7RTT9-1
SLC29A4	ENST00000297195.8	TSL:1	c.86A>T	p.Asp29Val	missense	Exon 2 of 11	ENSP00000297195.4	Q7RTT9-1
SLC29A4	ENST00000406453.3	TSL:1	c.86A>T	p.Asp29Val	missense	Exon 2 of 11	ENSP00000385845.3	Q7RTT9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111790

Other (OTH)

AF:

0.00

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

PhyloP100

6.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.4

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.98

Vest4

0.76

MutPred

0.47

Gain of sheet (P = 0.0266)

MVP

0.66

ClinPred

0.97

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.14

gMVP

0.74

Mutation Taster

=49/51

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over