7-5290792-C-A

Variant names:

• chr7-5290792-C-A
• NM_153247.4:c.230C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153247.4(SLC29A4):​c.230C>A​(p.Ala77Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC29A4 NM_153247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A4	NM_153247.4	c.230C>A	p.Ala77Asp	missense_variant	Exon 3 of 11	ENST00000396872.8	NP_694979.2
SLC29A4	NM_001040661.3	c.230C>A	p.Ala77Asp	missense_variant	Exon 3 of 11		NP_001035751.1
SLC29A4	NM_001300847.3	c.230C>A	p.Ala77Asp	missense_variant	Exon 3 of 11		NP_001287776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A4	ENST00000396872.8	c.230C>A	p.Ala77Asp	missense_variant	Exon 3 of 11	1	NM_153247.4	ENSP00000380081.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230C>A (p.A77D) alteration is located in exon 3 (coding exon 2) of the SLC29A4 gene. This alteration results from a C to A substitution at nucleotide position 230, causing the alanine (A) at amino acid position 77 to be replaced by an aspartic acid (D). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;T;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;.;D;D;D
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.8	.;M;.;M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.3	D;D;D;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.011	D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	.;D;.;D;D
Vest4		0.97, 0.95
MutPred		0.49		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.71
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.82
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-5330423;