19-46777119-A-G

Position:

• chr19-46777119-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_005628.3(SLC1A5):​c.1254-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,612,906 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (17 hom.)
• Consequence: SLC1A5 NM_005628.3 intron
• Scores: Splicing: ADA: 0.00003629
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.586

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-46777119-A-G is Benign according to our data. Variant chr19-46777119-A-G is described in ClinVar as [Benign]. Clinvar id is 3043445.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.1254-10T>C		intron_variant		ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.648-10T>C		intron_variant			NP_001138617.1
SLC1A5	NM_001145144.2	c.570-10T>C		intron_variant			NP_001138616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.1254-10T>C		intron_variant		1	NM_005628.3	ENSP00000444408.1
SLC1A5	ENST00000594991.5	c.726-10T>C		intron_variant		2		ENSP00000469265.1
SLC1A5	ENST00000434726.6	c.648-10T>C		intron_variant		2		ENSP00000406532.1
SLC1A5	ENST00000412532.6	c.570-10T>C		intron_variant		2		ENSP00000397924.1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 175 AN: 151884 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00854

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00218 AC: 544 AN: 249668 Hom.: 3 AF XY: 0.00256 AC XY: 346 AN XY: 134972

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000930

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00192 AC: 2808 AN: 1460904 Hom.: 17 Cov.: 31 AF XY: 0.00221 AC XY: 1606 AN XY: 726716

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00117

Gnomad4 ASJ exome AF: 0.00295

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0107

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.00115 AC: 175 AN: 152002 Hom.: 2 Cov.: 31 AF XY: 0.00124 AC XY: 92 AN XY: 74304

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00855

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00113 Hom.: 0

Bravo AF: 0.000903

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC1A5-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.014
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

Publications

LitVar

Other links and lift over

dbSNP: rs56363216; hg19: chr19-47280376;