6-25819139-G-T

Position:

• chr6-25819139-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A1	NM_005074.5	c.545C>A	p.Pro182His	missense_variant	6/13	ENST00000244527.10	NP_005065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A1	ENST00000244527.10	c.545C>A	p.Pro182His	missense_variant	6/13	5	NM_005074.5	ENSP00000244527.4
SLC17A1	ENST00000468082.1	c.545C>A	p.Pro182His	missense_variant	5/10	1		ENSP00000420546.1
SLC17A1	ENST00000476801.5	c.545C>A	p.Pro182His	missense_variant	6/12	2		ENSP00000420614.1
SLC17A1	ENST00000377886.6	n.545C>A		non_coding_transcript_exon_variant	6/12	5		ENSP00000367118.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455904 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

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	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;.
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.49	.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Benign	0.30	T
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	D
GERP RS		2.4
Varity_R		0.40
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs1581490142; hg19: chr6-25819367;