Genetic Variant SLC17A1:p.Trp458* (chr6-25798815-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005074.5(SLC17A1):c.1374G>A(p.Trp458*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,609,450 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 4 hom. )

Consequence

SLC17A1
NM_005074.5 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.97

Publications

5 publications found

Variant links:

Genes affected

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 6-25798815-C-T is Benign according to our data. Variant chr6-25798815-C-T is described in ClinVar as [Benign]. Clinvar id is 716025.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A1	NM_005074.5 link	c.1374G>A	p.Trp458*	stop_gained	Exon 12 of 13	ENST00000244527.10	NP_005065.2	Q14916-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A1	ENST00000244527.10 link	c.1374G>A	p.Trp458*	stop_gained	Exon 12 of 13	5	NM_005074.5	ENSP00000244527.4		Q14916-1

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

524

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000872

AC:

219

AN:

251144

AF XY:

0.000479

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000318

AC:

464

AN:

1457254

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

195

AN XY:

724720

show subpopulations

African (AFR)

AF:

0.0115

AC:

384

AN:

33434

American (AMR)

AF:

0.000559

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53200

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000902

AC:

AN:

1109112

Other (OTH)

AF:

0.000715

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00345

AC:

525

AN:

152196

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0115

AC:

477

AN:

41532

American (AMR)

AF:

0.00216

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68006

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00372

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.58

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

PhyloP100

3.0

Vest4

0.71

GERP RS

4.0

Mutation Taster

=187/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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6-25798815-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over