Genetic Variant CYLC1:p.Pro233Ser (chrX-83873405-C-T) – ACMG Classification: Benign (-7 pts)

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

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]

CYLC1 links:

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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
CYLC1	NM_021118.3 link	c.697C>T	p.Pro233Ser	missense_variant	Exon 4 of 5	ENST00000329312.5	NP_066941.1	P35663Q6PEK4
CYLC1	XM_005262086.5 link	c.694C>T	p.Pro232Ser	missense_variant	Exon 4 of 5		XP_005262143.1
CYLC1	NM_001271680.2 link	c.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
CYLC1	ENST00000329312.5 link	c.697C>T	p.Pro233Ser	missense_variant	Exon 4 of 5	1	NM_021118.3	ENSP00000331556.4		P35663
CYLC1	ENST00000621735.4 link	c.174+1835C>T		intron_variant	Intron 3 of 3	3		ENSP00000480907.1		A0A087WXC8

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

110849

Hom.:

Cov.:

AF XY:

0.0000599

AC XY:

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:

AN:

175068

Hom.:

AF XY:

0.000278

AC XY:

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.:

Cov.:

AF XY:

0.000117

AC XY:

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:

AN:

110900

Hom.:

Cov.:

AF XY:

0.0000598

AC XY:

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.:

Bravo

AF:

0.000144

ExAC

AF:

0.000198

AC:

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.067

DANN

Benign

0.27

DEOGEN2

Benign

0.00037

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.32

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.23

PROVEAN

Benign

1.3

REVEL

Benign

0.014

Sift

Benign

0.34

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.028

MVP

0.043

MPC

0.0020

ClinPred

0.022

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.

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