X-83871517-C-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BS2_Supporting

The NM_021118.3(CYLC1):c.124C>A(p.Gln42Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,201,089 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000017 ( 0 hom. 7 hem. )

Consequence

CYLC1
NM_021118.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.0310

Variant links:

Genes affected

CYLC1 (HGNC:2582): (cylicin 1) This gene encodes a sperm head cytoskeletal protein. The encoded protein is associated with the calyx of spermatozoa and spermatids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

CYLC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09265253).

BP6

Variant X-83871517-C-A is Benign according to our data. Variant chrX-83871517-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2660992.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAdExome4 at 7 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYLC1	NM_021118.3 link	c.124C>A	p.Gln42Lys	missense_variant	Exon 3 of 5	ENST00000329312.5	NP_066941.1	P35663Q6PEK4
CYLC1	NM_001271680.2 link	c.121C>A	p.Gln41Lys	missense_variant	Exon 3 of 4		NP_001258609.1	A0A087WXC8
CYLC1	XM_005262086.5 link	c.121C>A	p.Gln41Lys	missense_variant	Exon 3 of 5		XP_005262143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYLC1	ENST00000329312.5 link	c.124C>A	p.Gln42Lys	missense_variant	Exon 3 of 5	1	NM_021118.3	ENSP00000331556.4		P35663
CYLC1	ENST00000621735.4 link	c.121C>A	p.Gln41Lys	missense_variant	Exon 3 of 4	3		ENSP00000480907.1		A0A087WXC8

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110642

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33162

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000285

AC:

AN:

175267

Hom.:

AF XY:

0.0000656

AC XY:

AN XY:

60953

show subpopulations

Gnomad AFR exome

AF:

0.0000794

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000507

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1090447

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

357949

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000215

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110642

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33162

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000495

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.124C>A (p.Q42K) alteration is located in exon 3 (coding exon 3) of the CYLC1 gene. This alteration results from a C to A substitution at nucleotide position 124, causing the glutamine (Q) at amino acid position 42 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CYLC1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.87

DANN

Benign

0.75

DEOGEN2

Benign

0.0084

.;T

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.93

.;N

REVEL

Benign

0.041

Sift

Benign

0.38

.;T

Sift4G

Benign

0.10

T;T

Polyphen

0.58

.;P

Vest4

0.079

MutPred

0.16

.;Gain of methylation at Q42 (P = 0.0081);

MVP

0.15

MPC

0.0040

ClinPred

0.026

GERP RS

1.5

Varity_R

0.093

gMVP

0.016

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over