Genetic Variant NM_021118.3:c.575C>T (chrX-83873283-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.575C>T(p.Ser192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,089,159 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000064 ( 0 hom. 2 hem. )

Consequence

CYLC1
NM_021118.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.424

Publications

0 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=0.062182248).

BS2

High Hemizygotes in GnomAdExome4 at 2 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.575C>T	p.Ser192Leu	missense	Exon 4 of 5	NP_066941.1	P35663
	CYLC1	NM_001271680.2		c.174+1713C>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.575C>T	p.Ser192Leu	missense	Exon 4 of 5	ENSP00000331556.4	P35663
	CYLC1	ENST00000621735.4	TSL:3	c.174+1713C>T		intron	N/A	ENSP00000480907.1	A0A087WXC8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000587

AC:

AN:

170486

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000643

AC:

AN:

1089159

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

357001

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25842

American (AMR)

AF:

0.00

AC:

AN:

33729

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18931

East Asian (EAS)

AF:

0.00

AC:

AN:

30125

South Asian (SAS)

AF:

0.00

AC:

AN:

52229

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.00000835

AC:

AN:

838275

Other (OTH)

AF:

0.00

AC:

AN:

45632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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.:

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

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.0054

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.54

M_CAP

Benign

0.0092

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.42

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.038

Sift

Benign

1.0

Sift4G

Benign

0.25

Polyphen

0.11

Vest4

0.069

MutPred

0.31

Gain of helix (P = 0.0078)

MVP

0.043

MPC

0.0038

ClinPred

0.051

GERP RS

-0.25

Varity_R

0.059

gMVP

0.027

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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