X-83871517-C-A

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

17

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]

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
CYLC1NM_021118.3 linkc.124C>A p.Gln42Lys missense_variant Exon 3 of 5 ENST00000329312.5 NP_066941.1 P35663Q6PEK4
CYLC1NM_001271680.2 linkc.121C>A p.Gln41Lys missense_variant Exon 3 of 4 NP_001258609.1 A0A087WXC8
CYLC1XM_005262086.5 linkc.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
CYLC1ENST00000329312.5 linkc.124C>A p.Gln42Lys missense_variant Exon 3 of 5 1 NM_021118.3 ENSP00000331556.4 P35663
CYLC1ENST00000621735.4 linkc.121C>A p.Gln41Lys missense_variant Exon 3 of 4 3 ENSP00000480907.1 A0A087WXC8

Frequencies

GnomAD3 genomes
AF:
0.00000904
AC:
1
AN:
110642
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
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:
5
AN:
175267
Hom.:
0
AF XY:
0.0000656
AC XY:
4
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:
18
AN:
1090447
Hom.:
0
Cov.:
28
AF XY:
0.0000196
AC XY:
7
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:
1
AN:
110642
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
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:
6

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
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.87
DANN
Benign
0.75
DEOGEN2
Benign
0.0084
.;T
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.64
T;T
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.093
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
.;M
PrimateAI
Benign
0.29
T
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
T
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.

Other links and lift over

dbSNP: rs749731888; hg19: chrX-83126525; API