rs465563

Variant names:

• chr17-3610425-G-A
• rs465563
• ENST00000572919.1:n.*135C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-3610425-G-A
• chr17-3610425-G-C
• chr17-3610425-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572919.1(ENSG00000262304):​n.*135C>T variant causes a non coding transcript exon 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: ENSG00000262304 ENST00000572919.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 8 publications found

Genes affected

ENSG00000262304 (HGNC:):

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]

SHPK Gene-Disease associations (from GenCC):

• isolated sedoheptulokinase deficiency

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SHPK	NM_013276.4	c.*135C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000225519.5	NP_037408.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000262304	ENST00000572919.1	n.*135C>T		non_coding_transcript_exon_variant	Exon 7 of 14	5		ENSP00000461416.1
SHPK	ENST00000225519.5	c.*135C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_013276.4	ENSP00000225519.3
ENSG00000262304	ENST00000572919.1	n.*135C>T		3_prime_UTR_variant	Exon 7 of 14	5		ENSP00000461416.1

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

African (AFR) AF: 0.232 AC: 4415 AN: 19052

American (AMR) AF: 0.614 AC: 15757 AN: 25654

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 10285 AN: 15982

East Asian (EAS) AF: 0.661 AC: 23560 AN: 35620

South Asian (SAS) AF: 0.513 AC: 28228 AN: 54982

European-Finnish (FIN) AF: 0.738 AC: 24536 AN: 33228

Middle Eastern (MID) AF: 0.516 AC: 1987 AN: 3850

European-Non Finnish (NFE) AF: 0.675 AC: 369711 AN: 547436

Other (OTH) AF: 0.627 AC: 23178 AN: 36986

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

African (AFR) AF: 0.240 AC: 9980 AN: 41510

American (AMR) AF: 0.632 AC: 9664 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2237 AN: 3472

East Asian (EAS) AF: 0.674 AC: 3484 AN: 5170

South Asian (SAS) AF: 0.520 AC: 2504 AN: 4814

European-Finnish (FIN) AF: 0.751 AC: 7953 AN: 10584

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45837 AN: 67964

Other (OTH) AF: 0.605 AC: 1280 AN: 2116

Alfa AF: 0.627 Hom.: 40296

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs465563; hg19: chr17-3513719;