dbSNP rs146175657: SLC17A1:p.Arg167Pro (chr6-25819540-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005074.5(SLC17A1):c.500G>C(p.Arg167Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R167Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC17A1
NM_005074.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

0 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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A1	NM_005074.5 link	c.500G>C	p.Arg167Pro	missense_variant	Exon 5 of 13	ENST00000244527.10	NP_005065.2	Q14916-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC17A1	ENST00000244527.10 link	c.500G>C	p.Arg167Pro	missense_variant	Exon 5 of 13	5	NM_005074.5	ENSP00000244527.4	Q14916-1
SLC17A1	ENST00000468082.1 link	c.500G>C	p.Arg167Pro	missense_variant	Exon 4 of 10	1		ENSP00000420546.1	Q14916-2
SLC17A1	ENST00000476801.5 link	c.500G>C	p.Arg167Pro	missense_variant	Exon 5 of 12	2		ENSP00000420614.1	Q14916-1
SLC17A1	ENST00000377886.6 link	n.500G>C		non_coding_transcript_exon_variant	Exon 5 of 12	5		ENSP00000367118.2	E9PGW3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111908

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.70

D;D;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.4

M;M;M

PhyloP100

0.0060

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-6.1

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.68

MutPred

0.82

Loss of methylation at R167 (P = 0.0394);Loss of methylation at R167 (P = 0.0394);Loss of methylation at R167 (P = 0.0394);

MVP

0.75

MPC

0.59

ClinPred

0.84

GERP RS

-1.7

Varity_R

0.89

gMVP

0.91

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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rs146175657

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over