19-46778880-C-A

Variant names:

• chr19-46778880-C-A
• rs1305324732
• NM_005628.3:c.853G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005628.3(SLC1A5):​c.853G>T​(p.Val285Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,430,574 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15
• 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 2 ACMG points.

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

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.853G>T	p.Val285Leu	missense	Exon 5 of 8	NP_005619.1	Q15758-1
	SLC1A5	NM_001145145.2		c.247G>T	p.Val83Leu	missense	Exon 4 of 7	NP_001138617.1	Q15758-2
	SLC1A5	NM_001145144.2		c.169G>T	p.Val57Leu	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.853G>T	p.Val285Leu	missense	Exon 5 of 8	ENSP00000444408.1	Q15758-1
	SLC1A5	ENST00000926641.1		c.853G>T	p.Val285Leu	missense	Exon 5 of 8	ENSP00000596700.1
	SLC1A5	ENST00000891611.1		c.850G>T	p.Val284Leu	missense	Exon 5 of 8	ENSP00000561670.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000455 AC: 1 AN: 219678 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000119 AC: 17 AN: 1430574 Hom.: 0 Cov.: 34 AF XY: 0.00000847 AC XY: 6 AN XY: 708294

African (AFR) AF: 0.00 AC: 0 AN: 32940

American (AMR) AF: 0.00 AC: 0 AN: 41524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23432

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 79584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.0000155 AC: 17 AN: 1096906

Other (OTH) AF: 0.00 AC: 0 AN: 59178

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.54	P
Vest4		0.69
MutPred		0.79		Loss of ubiquitination at K288 (P = 0.1962)
MVP		0.78
MPC		1.3
ClinPred		0.73	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.65
gMVP		0.85
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs1305324732; hg19: chr19-47282137;