7-5287923-C-T

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

19

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]

Genome browser will be placed here

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
SLC29A4NM_153247.4 linkc.107C>T p.Ala36Val missense_variant Exon 2 of 11 ENST00000396872.8 NP_694979.2 Q7RTT9-1
SLC29A4NM_001040661.3 linkc.107C>T p.Ala36Val missense_variant Exon 2 of 11 NP_001035751.1 Q7RTT9-1
SLC29A4NM_001300847.3 linkc.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
SLC29A4ENST00000396872.8 linkc.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:
47
AN:
152240
Hom.:
0
Cov.:
34
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:
24
AN:
247202
Hom.:
0
AF XY:
0.0000818
AC XY:
11
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:
68
AN:
1459416
Hom.:
0
Cov.:
31
AF XY:
0.0000358
AC XY:
26
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:
47
AN:
152240
Hom.:
0
Cov.:
34
AF XY:
0.000336
AC XY:
25
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.:
0
Bravo
AF:
0.000321
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000107
AC:
13

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
T
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
N
LIST_S2
Benign
0.40
T;.;T;T;T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.017
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.1
.;L;.;L;L
PrimateAI
Benign
0.27
T
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
T
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.

Other links and lift over

dbSNP: rs200574190; hg19: chr7-5327554; API