rs1263407097

Variant names:

• chr19-46778831-C-A
• rs1263407097
• NM_005628.3:c.902G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-46778831-C-A
• chr19-46778831-C-G
• chr19-46778831-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005628.3(SLC1A5):​c.902G>T​(p.Arg301Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R301H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31398168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.902G>T	p.Arg301Leu	missense_variant	Exon 5 of 8	ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.296G>T	p.Arg99Leu	missense_variant	Exon 4 of 7		NP_001138617.1
SLC1A5	NM_001145144.2	c.218G>T	p.Arg73Leu	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.902G>T	p.Arg301Leu	missense_variant	Exon 5 of 8	1	NM_005628.3	ENSP00000444408.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246732 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133318

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: 0.00000897

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458182 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 725224

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: 0.00000180

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	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.;T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.43	N;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N;N;.;N
REVEL	Benign	0.047
Sift	Uncertain	0.025	D;D;.;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.17	B;.;.;.
Vest4		0.26
MutPred		0.52		Loss of methylation at R301 (P = 0.0357);.;.;.;
MVP		0.58
MPC		0.75
ClinPred		0.22	T
GERP RS		0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs1263407097; hg19: chr19-47282088;