17-3610425-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000572919.1(ENSG00000262304):​n.*135C>G variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 774568 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 394730

African (AFR) AF: 0.00 AC: 0 AN: 19068

American (AMR) AF: 0.00 AC: 0 AN: 25696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15998

East Asian (EAS) AF: 0.00 AC: 0 AN: 35634

South Asian (SAS) AF: 0.00 AC: 0 AN: 55136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3858

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 548854

Other (OTH) AF: 0.00 AC: 0 AN: 37062

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.55
PhyloP100		1.2

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;