Genetic Variant CYLC1:p.Ser118Phe (chrX-83873061-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_021118.3(CYLC1):c.353C>T(p.Ser118Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,085,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

CYLC1
NM_021118.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.327

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05746752).

BS2

High Hemizygotes in GnomAdExome4 at 4 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021118.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYLC1	NM_021118.3	MANE Select	c.353C>T	p.Ser118Phe	missense	Exon 4 of 5	NP_066941.1	P35663
	CYLC1	NM_001271680.2		c.174+1491C>T		intron	N/A	NP_001258609.1	A0A087WXC8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYLC1	ENST00000329312.5	TSL:1 MANE Select	c.353C>T	p.Ser118Phe	missense	Exon 4 of 5	ENSP00000331556.4	P35663
	CYLC1	ENST00000621735.4	TSL:3	c.174+1491C>T		intron	N/A	ENSP00000480907.1	A0A087WXC8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000242

AC:

AN:

165602

AF XY:

0.0000181

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1085116

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

354452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25504

American (AMR)

AF:

0.000153

AC:

AN:

32596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18748

East Asian (EAS)

AF:

0.00

AC:

AN:

29953

South Asian (SAS)

AF:

0.00

AC:

AN:

51068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40229

Middle Eastern (MID)

AF:

0.000247

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.00000358

AC:

AN:

837539

Other (OTH)

AF:

0.0000440

AC:

AN:

45433

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.97

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0078

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.45

M_CAP

Benign

0.0043

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

-0.33

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.012

Sift

Benign

0.28

Sift4G

Benign

0.17

Polyphen

0.053

Vest4

0.14

MutPred

0.19

Loss of phosphorylation at S118 (P = 0.0091)

MVP

0.043

MPC

0.0054

ClinPred

0.15

GERP RS

0.44

Varity_R

0.067

gMVP

0.025

Mutation Taster

=96/4

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

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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