chr6-25914573-G-T

Position:

• chr6-25914573-G-T

Variant summary

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

The NM_001286123.3(SLC17A2):​c.1302+7C>A variant causes a splice region, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC17A2 NM_001286123.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

SLC17A2 (HGNC:10930): (solute carrier family 17 member 2) Predicted to enable sialic acid transmembrane transporter activity. Predicted to be involved in sialic acid transport. Predicted to be located in membrane. Predicted to be active in lysosome. Predicted to be integral component of 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=0.182464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A2	NM_001286123.3	c.1302+7C>A		splice_region_variant, intron_variant		ENST00000377850.8	NP_001273052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A2	ENST00000377850.8	c.1302+7C>A		splice_region_variant, intron_variant		5	NM_001286123.3	ENSP00000367081.3
SLC17A2	ENST00000360488.7	c.1154+7C>A		splice_region_variant, intron_variant		1		ENSP00000353677.3
SLC17A2	ENST00000265425.3	c.1309C>A	p.Pro437Thr	missense_variant	10/11	5		ENSP00000265425.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1436046 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 716064

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.78
DEOGEN2	Benign	0.051	T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.070
Sift	Benign	0.36	T
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MutPred		0.28		Gain of glycosylation at P437 (P = 0.0462);
MVP		0.53
ClinPred		0.086	T
GERP RS		1.7
Varity_R		0.064

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: rs2071299; hg19: chr6-25914801;