rs465563

chr17-3610425-G-Achr17-3610425-G-Cchr17-3610425-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013276.4(SHPK):c.*135C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 924,906 control chromosomes in the GnomAD database, including 191,819 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (25981 hom., cov: 33)
  • Exomes 𝑓: 0.65 (165838 hom.)
• Consequence: SHPK NM_013276.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

Genes affected

SHPK (HGNC:1492): (sedoheptulokinase) The protein encoded by this gene has weak homology to several carbohydrate kinases, a class of proteins involved in the phosphorylation of sugars as they enter a cell, inhibiting return across the cell membrane. Sequence variation between this novel gene and known carbohydrate kinases suggests the possibility of a different substrate, cofactor or changes in kinetic properties distinguishing it from other carbohydrate kinases. The gene resides in a region commonly deleted in cystinosis patients, suggesting a role as a modifier for the cystinosis phenotype. The genomic region is also rich in Alu repetitive sequences, frequently involved in chromosomal rearrangements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHPK	NM_013276.4	c.*135C>T		3_prime_UTR_variant	7/7	ENST00000225519.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHPK	ENST00000225519.5	c.*135C>T		3_prime_UTR_variant	7/7	1	NM_013276.4	P1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83720 AN: 151998 Hom.: 25986 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.649 AC: 501657 AN: 772790 Hom.: 165838 Cov.: 10 AF XY: 0.646 AC XY: 254209 AN XY: 393778

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome AF: 0.550 AC: 83715 AN: 152116 Hom.: 25981 Cov.: 33 AF XY: 0.555 AC XY: 41248 AN XY: 74362

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.605

Alfa AF: 0.643 Hom.: 31902

Bravo AF: 0.530

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.6
Dann	Benign	0.51

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: rs465563; hg19: chr17-3513719;