chr7-22945391-A-T

Variant names:

• chr7-22945391-A-T
• rs2286492
• NM_032581.4:c.*198T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 14 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	NM_032581.4	MANE Select	c.*198T>A		3_prime_UTR	Exon 11 of 11	NP_115970.2
	HYCC1	NM_001363466.2		c.*800T>A		3_prime_UTR	Exon 12 of 12	NP_001350395.1	Q9BYI3-3
	HYCC1	NM_001363467.2		c.*758T>A		3_prime_UTR	Exon 12 of 12	NP_001350396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	ENST00000432176.7	TSL:1 MANE Select	c.*198T>A		3_prime_UTR	Exon 11 of 11	ENSP00000403396.2	Q9BYI3-1
	HYCC1	ENST00000440481.6	TSL:1	c.*800T>A		3_prime_UTR	Exon 11 of 11	ENSP00000397168.2	H7C0W7
	HYCC1	ENST00000905181.1		c.*198T>A		3_prime_UTR	Exon 11 of 11	ENSP00000575240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000454 AC: 2 AN: 440394 Hom.: 0 Cov.: 3 AF XY: 0.00000430 AC XY: 1 AN XY: 232418

African (AFR) AF: 0.00 AC: 0 AN: 12090

American (AMR) AF: 0.00 AC: 0 AN: 18452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13532

East Asian (EAS) AF: 0.0000649 AC: 2 AN: 30794

South Asian (SAS) AF: 0.00 AC: 0 AN: 42860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1934

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 266174

Other (OTH) AF: 0.00 AC: 0 AN: 25608

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
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

Other links and lift over

dbSNP: rs2286492; hg19: chr7-22985010;