NM_153247.4:c.411C>G

Variant names:

• chr7-5291233-C-G
• rs145785340
• NM_153247.4:c.411C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_153247.4(SLC29A4):​c.411C>G​(p.Thr137Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,612,040 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (3 hom.)
• Consequence: SLC29A4 NM_153247.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -3.11
• 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]

ENSG00000307592 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-5291233-C-G is Benign according to our data. Variant chr7-5291233-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2657269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.11 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.411C>G	p.Thr137Thr	synonymous	Exon 4 of 11	NP_694979.2	Q7RTT9-1
	SLC29A4	NM_001040661.3		c.411C>G	p.Thr137Thr	synonymous	Exon 4 of 11	NP_001035751.1	Q7RTT9-1
	SLC29A4	NM_001300847.3		c.411C>G	p.Thr137Thr	synonymous	Exon 4 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.411C>G	p.Thr137Thr	synonymous	Exon 4 of 11	ENSP00000380081.2	Q7RTT9-1
	SLC29A4	ENST00000297195.8	TSL:1	c.411C>G	p.Thr137Thr	synonymous	Exon 4 of 11	ENSP00000297195.4	Q7RTT9-1
	SLC29A4	ENST00000406453.3	TSL:1	c.411C>G	p.Thr137Thr	synonymous	Exon 4 of 11	ENSP00000385845.3	Q7RTT9-2

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000269 AC: 67 AN: 249434 AF XY: 0.000274

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000267

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000222 AC: 324 AN: 1459790 Hom.: 3 Cov.: 31 AF XY: 0.000234 AC XY: 170 AN XY: 726232

African (AFR) AF: 0.0000598 AC: 2 AN: 33436

American (AMR) AF: 0.000246 AC: 11 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00131 AC: 113 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52882

Middle Eastern (MID) AF: 0.00212 AC: 10 AN: 4706

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1111844

Other (OTH) AF: 0.000249 AC: 15 AN: 60242

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74432

African (AFR) AF: 0.0000481 AC: 2 AN: 41542

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000911 Hom.: 0

Bravo AF: 0.000238

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SLC29A4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.47
DANN	Benign	0.71
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs145785340; hg19: chr7-5330864;