chr7-5287900-C-G

Variant names:

• chr7-5287900-C-G
• rs140965974
• NM_153247.4:c.84C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153247.4(SLC29A4):​c.84C>G​(p.Phe28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F28F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC29A4 NM_153247.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21969602).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A4	NM_153247.4	MANE Select	c.84C>G	p.Phe28Leu	missense	Exon 2 of 11	NP_694979.2	Q7RTT9-1
	SLC29A4	NM_001040661.3		c.84C>G	p.Phe28Leu	missense	Exon 2 of 11	NP_001035751.1	Q7RTT9-1
	SLC29A4	NM_001300847.3		c.84C>G	p.Phe28Leu	missense	Exon 2 of 11	NP_001287776.1	Q7RTT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A4	ENST00000396872.8	TSL:1 MANE Select	c.84C>G	p.Phe28Leu	missense	Exon 2 of 11	ENSP00000380081.2	Q7RTT9-1
	SLC29A4	ENST00000297195.8	TSL:1	c.84C>G	p.Phe28Leu	missense	Exon 2 of 11	ENSP00000297195.4	Q7RTT9-1
	SLC29A4	ENST00000406453.3	TSL:1	c.84C>G	p.Phe28Leu	missense	Exon 2 of 11	ENSP00000385845.3	Q7RTT9-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248946 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459704 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726192

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4716

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60244

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.26
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.097
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.050	T
Polyphen		0.84	P
Vest4		0.42
MutPred		0.37		Loss of catalytic residue at F28 (P = 0.0181)
MVP		0.59
ClinPred		0.31	T
GERP RS		0.49
Varity_R		0.078
gMVP		0.73
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs140965974; hg19: chr7-5327531;