6-25819597-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005074.5(SLC17A1):c.443G>C(p.Gly148Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A1 NM_005074.5 missense, splice_region
• Scores: Splicing: ADA: 0.00006893
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.100

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A1	NM_005074.5	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	5/13	ENST00000244527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A1	ENST00000244527.10	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	5/13	5	NM_005074.5	P1
SLC17A1	ENST00000468082.1	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	4/10	1
SLC17A1	ENST00000476801.5	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	5/12	2		P1
SLC17A1	ENST00000377886.6	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant, NMD_transcript_variant	5/12	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 16, 2024

The c.443G>C (p.G148A) alteration is located in exon 5 (coding exon 4) of the SLC17A1 gene. This alteration results from a G to C substitution at nucleotide position 443, causing the glycine (G) at amino acid position 148 to be replaced by an alanine (A). 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	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	13
Dann	Benign	0.73
DEOGEN2	Benign	0.39	T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.066	N
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.2	M;M;M
MutationTaster	Benign	0.95	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.68	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.39
MutPred		0.87		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.56
MPC		0.31
ClinPred		0.65	D
GERP RS		0.89
Varity_R		0.079
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000069
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-25819825;