rs1060043

Variant names:

• chr19-46775681-G-A
• rs1060043
• NM_005628.3:c.1455C>T

Your query was ambiguous. Multiple possible variants found:

• 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:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]

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 rank	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.1455C>T	p.Tyr485Tyr	synonymous_variant	Exon 8 of 8	ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.849C>T	p.Tyr283Tyr	synonymous_variant	Exon 7 of 7		NP_001138617.1
SLC1A5	NM_001145144.2	c.771C>T	p.Tyr257Tyr	synonymous_variant	Exon 8 of 8		NP_001138616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.1455C>T	p.Tyr485Tyr	synonymous_variant	Exon 8 of 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;