rs1060043

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.960

Publications

22 publications found

Variant links:

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]

SLC1A5 links:

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]

FKRP Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2I
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Ambry Genetics
muscular dystrophy-dystroglycanopathy type B5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
myopathy caused by variation in FKRP
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FKRP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.1455C>T	p.Tyr485Tyr	synonymous_variant	Exon 8 of 8	ENST00000542575.6	NP_005619.1	Q15758-1Q59ES3
SLC1A5	NM_001145145.2 link	c.849C>T	p.Tyr283Tyr	synonymous_variant	Exon 7 of 7		NP_001138617.1	Q15758-2
SLC1A5	NM_001145144.2 link	c.771C>T	p.Tyr257Tyr	synonymous_variant	Exon 8 of 8		NP_001138616.1	Q15758-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6 link	c.1455C>T	p.Tyr485Tyr	synonymous_variant	Exon 8 of 8	1	NM_005628.3	ENSP00000444408.1		Q15758-1

Frequencies

GnomAD3 genomes

AF:

0.0811

AC:

12320

AN:

151942

Hom.:

642

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0950

AC:

23725

AN:

249680

AF XY:

0.100

show subpopulations

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 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.:

AF XY:

0.0968

AC XY:

70406

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0230

AC:

769

AN:

33480

American (AMR)

AF:

0.0482

AC:

2156

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4315

AN:

26136

East Asian (EAS)

AF:

0.0196

AC:

777

AN:

39698

South Asian (SAS)

AF:

0.112

AC:

9651

AN:

86254

European-Finnish (FIN)

AF:

0.180

AC:

9618

AN:

53414

Middle Eastern (MID)

AF:

0.148

AC:

854

AN:

5768

European-Non Finnish (NFE)

AF:

0.0946

AC:

105163

AN:

1111952

Other (OTH)

AF:

0.0938

AC:

5663

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6669

13337

20006

26674

33343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3656

7312

10968

14624

18280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0810

AC:

12314

AN:

152060

Hom.:

641

Cov.:

AF XY:

0.0850

AC XY:

6318

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0272

AC:

1128

AN:

41528

American (AMR)

AF:

0.0658

AC:

1003

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

565

AN:

3468

East Asian (EAS)

AF:

0.0168

AC:

AN:

5168

South Asian (SAS)

AF:

0.102

AC:

489

AN:

4810

European-Finnish (FIN)

AF:

0.182

AC:

1925

AN:

10560

Middle Eastern (MID)

AF:

0.151

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.101

AC:

6834

AN:

67960

Other (OTH)

AF:

0.0849

AC:

179

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

563

1126

1688

2251

2814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0908

Hom.:

923

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

(source)

DANN

Benign

0.44

PhyloP100

-0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over