dbSNP rs1581490142: SLC17A1:p.Pro182His (chr6-25819139-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005074.5(SLC17A1):c.545C>A(p.Pro182His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC17A1
NM_005074.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A1	NM_005074.5 link	c.545C>A	p.Pro182His	missense_variant	Exon 6 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.545C>A	p.Pro182His	missense_variant	Exon 6 of 13	5	NM_005074.5	ENSP00000244527.4	Q14916-1
SLC17A1	ENST00000468082.1 link	c.545C>A	p.Pro182His	missense_variant	Exon 5 of 10	1		ENSP00000420546.1	Q14916-2
SLC17A1	ENST00000476801.5 link	c.545C>A	p.Pro182His	missense_variant	Exon 6 of 12	2		ENSP00000420614.1	Q14916-1
SLC17A1	ENST00000377886.6 link	n.545C>A		non_coding_transcript_exon_variant	Exon 6 of 12	5		ENSP00000367118.2	E9PGW3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724162

African (AFR)

AF:

0.00

AC:

AN:

33178

American (AMR)

AF:

0.00

AC:

AN:

43458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

84706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110040

Other (OTH)

AF:

0.00

AC:

AN:

60090

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.545C>A (p.P182H) alteration is located in exon 6 (coding exon 5) of the SLC17A1 gene. This alteration results from a C to A substitution at nucleotide position 545, causing the proline (P) at amino acid position 182 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;.

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.49

.;T;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;M;M

PhyloP100

1.2

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.029

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.52

MutPred

0.61

Gain of catalytic residue at P182 (P = 0.0133);Gain of catalytic residue at P182 (P = 0.0133);Gain of catalytic residue at P182 (P = 0.0133);

MVP

0.60

MPC

0.53

ClinPred

0.88

GERP RS

2.4

Varity_R

0.40

gMVP

0.43

Mutation Taster

=94/6

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over