X-83873405-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_021118.3(CYLC1):​c.697C>T​(p.Pro233Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,202,076 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P233L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.00011 ( 0 hom. 42 hem. )

Consequence

CYLC1
NM_021118.3 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.606
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 Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0046162307).
BP6
Variant X-83873405-C-T is Benign according to our data. Variant chrX-83873405-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660994.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 2 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.697C>T p.Pro233Ser missense_variant Exon 4 of 5 ENST00000329312.5 NP_066941.1 P35663Q6PEK4
CYLC1XM_005262086.5 linkc.694C>T p.Pro232Ser missense_variant Exon 4 of 5 XP_005262143.1
CYLC1NM_001271680.2 linkc.174+1835C>T intron_variant Intron 3 of 3 NP_001258609.1 A0A087WXC8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYLC1ENST00000329312.5 linkc.697C>T p.Pro233Ser missense_variant Exon 4 of 5 1 NM_021118.3 ENSP00000331556.4 P35663
CYLC1ENST00000621735.4 linkc.174+1835C>T intron_variant Intron 3 of 3 3 ENSP00000480907.1 A0A087WXC8

Frequencies

GnomAD3 genomes
AF:
0.000126
AC:
14
AN:
110849
Hom.:
0
Cov.:
22
AF XY:
0.0000599
AC XY:
2
AN XY:
33363
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00397
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:
0.000286
AC:
50
AN:
175068
Hom.:
0
AF XY:
0.000278
AC XY:
17
AN XY:
61204
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00362
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000233
GnomAD4 exome
AF:
0.000107
AC:
117
AN:
1091176
Hom.:
0
Cov.:
30
AF XY:
0.000117
AC XY:
42
AN XY:
357776
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00372
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000109
GnomAD4 genome
AF:
0.000126
AC:
14
AN:
110900
Hom.:
0
Cov.:
22
AF XY:
0.0000598
AC XY:
2
AN XY:
33424
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00398
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000104
Hom.:
5
Bravo
AF:
0.000144
ExAC
AF:
0.000198
AC:
24

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

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
0.087
BayesDel_addAF
Benign
-0.87
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.067
DANN
Benign
0.27
DEOGEN2
Benign
0.00037
T
FATHMM_MKL
Benign
0.0094
N
LIST_S2
Benign
0.32
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.0046
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
1.3
N
REVEL
Benign
0.014
Sift
Benign
0.34
T
Sift4G
Benign
0.65
T
Polyphen
0.0
B
Vest4
0.028
MVP
0.043
MPC
0.0020
ClinPred
0.022
T
GERP RS
1.3
Varity_R
0.031
gMVP
0.0087

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: rs201422295; hg19: chrX-83128413; COSMIC: COSV61411057; API