7-22942099-CTCTG-C

Position:

• chr7-22942099-CTCTG-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_032581.4(HYCC1):​c.*3486_*3489del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.00038 (0 hom., cov: 32)
• Consequence: HYCC1 NM_032581.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.804

Genes affected

HYCC1 (HGNC:24587): (hyccin PI4KA lipid kinase complex subunit 1) The protein encoded by this gene may play a part in the beta-catenin/Lef signaling pathway. Expression of this gene is down-regulated by beta-catenin. Defects in this gene are a cause of hypomyelination with congenital cataract (HCC). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000381 (58/152166) while in subpopulation AMR AF= 0.00314 (48/15276). AF 95% confidence interval is 0.00243. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	NM_032581.4	c.*3486_*3489del		3_prime_UTR_variant	11/11	ENST00000432176.7	NP_115970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000432176.7	c.*3486_*3489del		3_prime_UTR_variant	11/11	1	NM_032581.4	ENSP00000403396

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00383

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

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000471 AC XY: 35 AN XY: 74378

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000888

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypomyelination and Congenital Cataract Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs545140159; hg19: chr7-22981718;