7-22960423-GA-GAA

Variant names:

• chr7-22960423-G-GA
• rs1554269900
• NM_032581.4:c.832-9dupT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_032581.4(HYCC1):​c.832-9dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HYCC1 NM_032581.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0720
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 7-22960423-G-GA is Benign according to our data. Variant chr7-22960423-G-GA is described in ClinVar as Benign. ClinVar VariationId is 468355.Status of the report is criteria_provided_single_submitter, 1 stars.

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.832-9dupT		intron	N/A	NP_115970.2
	HYCC1	NM_001363466.2		c.832-9dupT		intron	N/A	NP_001350395.1	Q9BYI3-3
	HYCC1	NM_001363467.2		c.832-9dupT		intron	N/A	NP_001350396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	ENST00000432176.7	TSL:1 MANE Select	c.832-9_832-8insT		intron	N/A	ENSP00000403396.2	Q9BYI3-1
	HYCC1	ENST00000440481.6	TSL:1	c.400-9_400-8insT		intron	N/A	ENSP00000397168.2	H7C0W7
	HYCC1	ENST00000905181.1		c.832-9_832-8insT		intron	N/A	ENSP00000575240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456630 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725028

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108294

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hypomyelination and Congenital Cataract (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.072

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: rs1554269900; hg19: chr7-23000042;