7-22942588-T-C

Position:

• chr7-22942588-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032581.4(HYCC1):​c.*3001A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,988 control chromosomes in the GnomAD database, including 11,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11747 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HYCC1 NM_032581.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-22942588-T-C is Benign according to our data. Variant chr7-22942588-T-C is described in ClinVar as [Benign]. Clinvar id is 359725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	NM_032581.4	c.*3001A>G		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.*3001A>G		3_prime_UTR_variant	11/11	1	NM_032581.4	ENSP00000403396

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59792 AN: 151864 Hom.: 11735 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.394 AC: 59840 AN: 151982 Hom.: 11747 Cov.: 32 AF XY: 0.393 AC XY: 29186 AN XY: 74270

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.364

Alfa AF: 0.384 Hom.: 1787

Bravo AF: 0.396

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypomyelination and Congenital Cataract Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.64

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: rs2286495; hg19: chr7-22982207;