NM_153247.4:c.86A>G

Variant names:

• chr7-5287902-A-G
• rs145276221
• NM_153247.4:c.86A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_153247.4(SLC29A4):​c.86A>G​(p.Asp29Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00277 in 1,612,106 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D29N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0028 (8 hom.)
• Consequence: SLC29A4 NM_153247.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.88
• Publications: 6 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007852465).
• BP6: Variant 7-5287902-A-G is Benign according to our data. Variant chr7-5287902-A-G is described in ClinVar as Benign. ClinVar VariationId is 3044053.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 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.86A>G	p.Asp29Gly	missense	Exon 2 of 11	NP_694979.2	Q7RTT9-1
	SLC29A4	NM_001040661.3		c.86A>G	p.Asp29Gly	missense	Exon 2 of 11	NP_001035751.1	Q7RTT9-1
	SLC29A4	NM_001300847.3		c.86A>G	p.Asp29Gly	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.86A>G	p.Asp29Gly	missense	Exon 2 of 11	ENSP00000380081.2	Q7RTT9-1
	SLC29A4	ENST00000297195.8	TSL:1	c.86A>G	p.Asp29Gly	missense	Exon 2 of 11	ENSP00000297195.4	Q7RTT9-1
	SLC29A4	ENST00000406453.3	TSL:1	c.86A>G	p.Asp29Gly	missense	Exon 2 of 11	ENSP00000385845.3	Q7RTT9-2

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152248 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00245 AC: 609 AN: 248964 AF XY: 0.00236

Gnomad AFR exome AF: 0.000752

Gnomad AMR exome AF: 0.00328

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00279

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00281 AC: 4099 AN: 1459740 Hom.: 8 Cov.: 31 AF XY: 0.00272 AC XY: 1978 AN XY: 726206

African (AFR) AF: 0.000658 AC: 22 AN: 33426

American (AMR) AF: 0.00324 AC: 145 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 377 AN: 26124

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.0000756 AC: 4 AN: 52876

Middle Eastern (MID) AF: 0.00191 AC: 9 AN: 4716

European-Non Finnish (NFE) AF: 0.00298 AC: 3313 AN: 1111788

Other (OTH) AF: 0.00380 AC: 229 AN: 60246

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152366 Hom.: 1 Cov.: 34 AF XY: 0.00227 AC XY: 169 AN XY: 74512

African (AFR) AF: 0.000625 AC: 26 AN: 41590

American (AMR) AF: 0.00458 AC: 70 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 68038

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00313 Hom.: 1

Bravo AF: 0.00257

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00171 AC: 207

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC29A4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.89	N
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.044	D
Polyphen		0.78	P
Vest4		0.65
MVP		0.76
ClinPred		0.031	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.12
gMVP		0.72
Mutation Taster		=55/45	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: rs145276221; hg19: chr7-5327533;