Genetic Variant HYCC1:c.*3753C>T (chr7-22941836-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032581.4(HYCC1):c.*3753C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 152,186 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

HYCC1
NM_032581.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.39

Publications

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

HYCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 7-22941836-G-A is Benign according to our data. Variant chr7-22941836-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 359720.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00342 (520/152186) while in subpopulation SAS AF = 0.0083 (40/4820). AF 95% confidence interval is 0.00626. There are 3 homozygotes in GnomAd4. There are 272 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYCC1	NM_032581.4	MANE Select	c.*3753C>T	3_prime_UTR	Exon 11 of 11	NP_115970.2
HYCC1	NM_001363466.2		c.*4355C>T	3_prime_UTR	Exon 12 of 12	NP_001350395.1	Q9BYI3-3
HYCC1	NM_001363467.2		c.*4313C>T	3_prime_UTR	Exon 12 of 12	NP_001350396.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYCC1	ENST00000432176.7	TSL:1 MANE Select	c.*3753C>T	3_prime_UTR	Exon 11 of 11	ENSP00000403396.2	Q9BYI3-1
HYCC1	ENST00000440481.6	TSL:1	c.*4355C>T	3_prime_UTR	Exon 11 of 11	ENSP00000397168.2	H7C0W7
HYCC1	ENST00000679826.1		c.*3753C>T	3_prime_UTR	Exon 12 of 12	ENSP00000505460.1	A0A7P0T943

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

520

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.00472

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00421

Gnomad OTH

AF:

0.00431

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.00342

AC:

520

AN:

152186

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

272

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41554

American (AMR)

AF:

0.00485

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00472

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00421

AC:

286

AN:

67978

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000639

Hom.:

Bravo

AF:

0.00335

Asia WGS

AF:

0.00175

AC:

AN:

3446

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypomyelination and Congenital Cataract (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over