3-72817217-TACATGCACTTA-T

Position:

• chr3-72817217-TACATGCACTTA-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018130.3(SHQ1):​c.882+2_882+12del variant causes a splice donor, splice donor 5th base, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHQ1 NM_018130.3 splice_donor, splice_donor_5th_base, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.48

Genes affected

SHQ1 (HGNC:25543): (SHQ1, H/ACA ribonucleoprotein assembly factor) SHQ1 assists in the assembly of H/ACA-box ribonucleoproteins that function in the processing of ribosomal RNAs, modification of spliceosomal small nuclear RNAs, and stabilization of telomerase (see MIM 602322) (Grozdanov et al., 2009 [PubMed 19383767]).[supplied by OMIM, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHQ1	NM_018130.3	c.882+2_882+12del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		ENST00000325599.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHQ1	ENST00000325599.13	c.882+2_882+12del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		1	NM_018130.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

SHQ1-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 04, 2024

The SHQ1 c.882+2_882+12del11 variant is predicted to result in a deletion affecting a canonical splice site. Based on available splicing prediction programs (Alamut Visual Plus v1.6.1) this variant is predicted to abolish the consensus splice donor site; however, to date this prediction has not been proven by functional studies. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. No other SHQ1 splicing variants have been reported in the literature to date, and loss-of-function is not an well-established mechanism of disease for SHQ1-related disorder(s) (Human Gene Mutation Database, http://www.hgmd.cf.ac.uk/ac/index.php). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-72866368;