NM_032581.4:c.992-6203T>C

Variant names:

• chr7-22952366-A-G
• rs10240716
• NM_032581.4:c.992-6203T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032581.4(HYCC1):​c.992-6203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,004 control chromosomes in the GnomAD database, including 4,825 homozygotes. 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: 𝑓 0.25 (4825 hom., cov: 33)
• Consequence: HYCC1 NM_032581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 2 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	NM_032581.4	MANE Select	c.992-6203T>C		intron	N/A	NP_115970.2
	HYCC1	NM_001363466.2		c.992-5119T>C		intron	N/A	NP_001350395.1
	HYCC1	NM_001363467.2		c.992-5119T>C		intron	N/A	NP_001350396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	ENST00000432176.7	TSL:1 MANE Select	c.992-6203T>C		intron	N/A	ENSP00000403396.2
	HYCC1	ENST00000440481.6	TSL:1	c.560-5119T>C		intron	N/A	ENSP00000397168.2
	HYCC1	ENST00000681766.1		c.938-6203T>C		intron	N/A	ENSP00000505161.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37506 AN: 151886 Hom.: 4820 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.247 AC: 37538 AN: 152004 Hom.: 4825 Cov.: 33 AF XY: 0.249 AC XY: 18475 AN XY: 74302

African (AFR) AF: 0.207 AC: 8599 AN: 41516

American (AMR) AF: 0.269 AC: 4090 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 987 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2448 AN: 5172

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4822

European-Finnish (FIN) AF: 0.206 AC: 2187 AN: 10596

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16792 AN: 67890

Other (OTH) AF: 0.238 AC: 502 AN: 2110

Alfa AF: 0.238 Hom.: 574

Bravo AF: 0.251

Asia WGS AF: 0.356 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs10240716; hg19: chr7-22991985;