19-46778831-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005628.3(SLC1A5):​c.902G>C​(p.Arg301Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: 0.0000075 (0 hom.)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28878468).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005628.3. 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
	SLC1A5	NM_005628.3	MANE Select	c.902G>C	p.Arg301Pro	missense	Exon 5 of 8	NP_005619.1	Q15758-1
	SLC1A5	NM_001145145.2		c.296G>C	p.Arg99Pro	missense	Exon 4 of 7	NP_001138617.1	Q15758-2
	SLC1A5	NM_001145144.2		c.218G>C	p.Arg73Pro	missense	Exon 5 of 8	NP_001138616.1	Q15758-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A5	ENST00000542575.6	TSL:1 MANE Select	c.902G>C	p.Arg301Pro	missense	Exon 5 of 8	ENSP00000444408.1	Q15758-1
	SLC1A5	ENST00000926641.1		c.902G>C	p.Arg301Pro	missense	Exon 5 of 8	ENSP00000596700.1
	SLC1A5	ENST00000891611.1		c.899G>C	p.Arg300Pro	missense	Exon 5 of 8	ENSP00000561670.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458184 Hom.: 0 Cov.: 34 AF XY: 0.00000689 AC XY: 5 AN XY: 725226

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000991 AC: 11 AN: 1110166

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N
PhyloP100		1.8
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.096
Sift	Uncertain	0.021	D
Sift4G	Benign	0.096	T
Polyphen		0.0020	B
Vest4		0.35
MutPred		0.53		Loss of methylation at R301 (P = 0.0357)
MVP		0.59
MPC		0.83
ClinPred		0.60	D
GERP RS		0.034
Varity_R		0.79
gMVP		0.90
Mutation Taster		=70/30	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: rs1263407097; hg19: chr19-47282088;