6-25812922-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.806C>G(p.Thr269Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. T269I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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=0.16115472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A1	NM_005074.5	c.806C>G	p.Thr269Ser	missense_variant	8/13	ENST00000244527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A1	ENST00000244527.10	c.806C>G	p.Thr269Ser	missense_variant	8/13	5	NM_005074.5	P1
SLC17A1	ENST00000468082.1	c.735+173C>G		intron_variant		1
SLC17A1	ENST00000476801.5	c.806C>G	p.Thr269Ser	missense_variant	8/12	2		P1
SLC17A1	ENST00000377886.6	c.*57C>G		3_prime_UTR_variant, NMD_transcript_variant	7/12	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	13
Dann	Benign	0.91
DEOGEN2	Benign	0.078	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.035	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.095
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.30	B;B
Vest4		0.13
MutPred		0.50		Gain of glycosylation at T269 (P = 0.0451);Gain of glycosylation at T269 (P = 0.0451);
MVP		0.59
MPC		0.099
ClinPred		0.35	T
GERP RS		3.7
Varity_R		0.079
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs1165196; hg19: chr6-25813150;