6-25798909-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005074.5(SLC17A1):c.1280C>G(p.Ser427Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.543

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24895865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A1	NM_005074.5	c.1280C>G	p.Ser427Cys	missense_variant	12/13	ENST00000244527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A1	ENST00000244527.10	c.1280C>G	p.Ser427Cys	missense_variant	12/13	5	NM_005074.5	P1
SLC17A1	ENST00000468082.1	c.1118C>G	p.Ser373Cys	missense_variant	10/10	1
SLC17A1	ENST00000476801.5	c.1280C>G	p.Ser427Cys	missense_variant	12/12	2		P1
SLC17A1	ENST00000377886.6	c.*531C>G		3_prime_UTR_variant, NMD_transcript_variant	11/12	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428344 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706106

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: 0.0000170

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

May 03, 2023

The c.1280C>G (p.S427C) alteration is located in exon 12 (coding exon 11) of the SLC17A1 gene. This alteration results from a C to G substitution at nucleotide position 1280, causing the serine (S) at amino acid position 427 to be replaced by a cysteine (C). 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	Benign	0.15
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	13
Dann	Benign	0.94
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.027	N
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M;M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.086	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.43
MutPred		0.53		Loss of disorder (P = 0.0627);Loss of disorder (P = 0.0627);.;
MVP		0.67
MPC		0.38
ClinPred		0.47	T
GERP RS		-0.34
Varity_R		0.073
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs1763668418; hg19: chr6-25799137;