19-46787917-G-T

Variant names:

• chr19-46787917-G-T
• rs3027956
• NM_005628.3:c.49C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005628.3(SLC1A5):​c.49C>A​(p.Pro17Thr) 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 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. P17A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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]

ENSG00000275719 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07233885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 8	ENST00000542575.6	NP_005619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 8	1	NM_005628.3	ENSP00000444408.1
ENSG00000275719	ENST00000612522.1	n.103G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000275719	ENST00000617006.1	n.103G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1420774 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 703574

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.083
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0020	B
Vest4		0.062
MutPred		0.15		Loss of loop (P = 0.0374);
MVP		0.58
MPC		0.65
ClinPred		0.24	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.040
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs3027956; hg19: chr19-47291174;