Genetic Variant NM_153247.4:c.439C>T (chr7-5291716-C-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.439C>T(p.Leu147Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,462 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC29A4
NM_153247.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

Publications

0 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:

ENSG00000307592 (HGNC:):

ENSG00000307592 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.439C>T	p.Leu147Phe	missense	Exon 5 of 11	NP_694979.2	Q7RTT9-1
SLC29A4	NM_001040661.3		c.439C>T	p.Leu147Phe	missense	Exon 5 of 11	NP_001035751.1	Q7RTT9-1
SLC29A4	NM_001300847.3		c.416-14C>T		intron	N/A	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.439C>T	p.Leu147Phe	missense	Exon 5 of 11	ENSP00000380081.2	Q7RTT9-1
SLC29A4	ENST00000297195.8	TSL:1	c.439C>T	p.Leu147Phe	missense	Exon 5 of 11	ENSP00000297195.4	Q7RTT9-1
SLC29A4	ENST00000406453.3	TSL:1	c.416-14C>T		intron	N/A	ENSP00000385845.3	Q7RTT9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459462

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111700

Other (OTH)

AF:

0.00

AC:

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.20

Sift

Benign

0.065

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.80

MutPred

0.49

Gain of helix (P = 0.1736)

MVP

0.61

ClinPred

0.99

GERP RS

3.5

Varity_R

0.47

gMVP

0.65

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over