rs765008475

Variant names:

• chr19-46778904-C-A
• rs765008475
• NM_005628.3:c.829G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-46778904-C-A
• chr19-46778904-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005628.3(SLC1A5):​c.829G>T​(p.Ala277Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000712 in 1,404,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A277T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13

Genes affected

SLC1A5 (HGNC:10943): (solute carrier family 1 member 5) The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus (Larriba et al., 2001 [PubMed 11781704]).[supplied by OMIM, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.829G>T	p.Ala277Ser	missense_variant	Exon 5 of 8	ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.223G>T	p.Ala75Ser	missense_variant	Exon 4 of 7		NP_001138617.1
SLC1A5	NM_001145144.2	c.145G>T	p.Ala49Ser	missense_variant	Exon 5 of 8		NP_001138616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.829G>T	p.Ala277Ser	missense_variant	Exon 5 of 8	1	NM_005628.3	ENSP00000444408.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000494 AC: 1 AN: 202524 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 107056

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404290 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 692304

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: 9.23e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.85
DEOGEN2	Benign	0.14	T;.;T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N;N;.;N
REVEL	Benign	0.28
Sift	Benign	0.87	T;T;.;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.31	B;.;.;.
Vest4		0.51
MutPred		0.76		Loss of stability (P = 0.3254);.;.;.;
MVP		0.72
MPC		1.4
ClinPred		0.83	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs765008475; hg19: chr19-47282161;