rs1060043

Positions:

• chr19-46775681-G-A
• chr19-46775681-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005628.3(SLC1A5):​c.1455C>T​(p.Tyr485Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 1,613,874 control chromosomes in the GnomAD database, including 8,135 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.081 (641 hom., cov: 31)
  • Exomes 𝑓: 0.095 (7494 hom.)
• Consequence: SLC1A5 NM_005628.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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]

FKRP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.1455C>T	p.Tyr485Tyr	synonymous_variant	8/8	ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.849C>T	p.Tyr283Tyr	synonymous_variant	7/7		NP_001138617.1
SLC1A5	NM_001145144.2	c.771C>T	p.Tyr257Tyr	synonymous_variant	8/8		NP_001138616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.1455C>T	p.Tyr485Tyr	synonymous_variant	8/8	1	NM_005628.3	ENSP00000444408.1

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12320 AN: 151942 Hom.: 642 Cov.: 31

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0849

GnomAD3 exomes AF: 0.0950 AC: 23725 AN: 249680 Hom.: 1439 AF XY: 0.100 AC XY: 13502 AN XY: 135084

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.0465

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.0156

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.0951 AC: 138966 AN: 1461814 Hom.: 7494 Cov.: 35 AF XY: 0.0968 AC XY: 70406 AN XY: 727212

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.0482

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0196

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.0946

Gnomad4 OTH exome AF: 0.0938

GnomAD4 genome AF: 0.0810 AC: 12314 AN: 152060 Hom.: 641 Cov.: 31 AF XY: 0.0850 AC XY: 6318 AN XY: 74306

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0849

Alfa AF: 0.0979 Hom.: 795

Bravo AF: 0.0688

Asia WGS AF: 0.0620 AC: 216 AN: 3478

EpiCase AF: 0.0991

EpiControl AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.16
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1060043; hg19: chr19-47278938; COSMIC: COSV69467359; COSMIC: COSV69467359;