19-46777366-C-A

Variant names:

• chr19-46777366-C-A
• NM_005628.3:c.1098G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005628.3(SLC1A5):​c.1098G>T​(p.Glu366Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.613
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

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.1098G>T	p.Glu366Asp	missense	Exon 6 of 8	NP_005619.1	Q15758-1
	SLC1A5	NM_001145145.2		c.492G>T	p.Glu164Asp	missense	Exon 5 of 7	NP_001138617.1	Q15758-2
	SLC1A5	NM_001145144.2		c.414G>T	p.Glu138Asp	missense	Exon 6 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.1098G>T	p.Glu366Asp	missense	Exon 6 of 8	ENSP00000444408.1	Q15758-1
	SLC1A5	ENST00000926641.1		c.1116G>T	p.Glu372Asp	missense	Exon 6 of 8	ENSP00000596700.1
	SLC1A5	ENST00000891611.1		c.1095G>T	p.Glu365Asp	missense	Exon 6 of 8	ENSP00000561670.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	Benign	0.16
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.096
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.61
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.26
Sift	Benign	0.070	T
Sift4G	Benign	0.10	T
Polyphen		0.090	B
Vest4		0.67
MutPred		0.66		Loss of ubiquitination at K362 (P = 0.1083)
MVP		0.81
MPC		1.4
ClinPred		0.88	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.75
Mutation Taster		=42/58	disease causing

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

hg19: chr19-47280623;