Genetic Variant HYCC1:c.*198T>A (chr7-22945391-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032581.4(HYCC1):c.*198T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000454 in 440,394 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

HYCC1
NM_032581.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

14 publications found

Variant links:

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]

HYCC1 Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 5
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

HYCC1 links:

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ACMG classification

Classification was made for transcript

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYCC1	NM_032581.4 link	c.*198T>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000432176.7	NP_115970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000432176.7 link	c.*198T>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_032581.4	ENSP00000403396.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000454

AC:

AN:

440394

Hom.:

Cov.:

AF XY:

0.00000430

AC XY:

AN XY:

232418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12090

American (AMR)

AF:

0.00

AC:

AN:

18452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13532

East Asian (EAS)

AF:

0.0000649

AC:

AN:

30794

South Asian (SAS)

AF:

0.00

AC:

AN:

42860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1934

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

266174

Other (OTH)

AF:

0.00

AC:

AN:

25608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.63

PhyloP100

-0.058

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over