NM_021118.3:c.698C>T

Variant names:

• chrX-83873406-C-T
• rs745675150
• NM_021118.3:c.698C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_021118.3(CYLC1):​c.698C>T​(p.Pro233Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000949 in 1,201,705 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P233S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.00010 (0 hom. 42 hem.)
• Consequence: CYLC1 NM_021118.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.17
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.02347666).
• BS2: High Hemizygotes in GnomAd4 at 3 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.698C>T	p.Pro233Leu	missense	Exon 4 of 5	NP_066941.1	P35663
	CYLC1	NM_001271680.2		c.174+1836C>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.698C>T	p.Pro233Leu	missense	Exon 4 of 5	ENSP00000331556.4	P35663
	CYLC1	ENST00000621735.4	TSL:3	c.174+1836C>T		intron	N/A	ENSP00000480907.1	A0A087WXC8

Frequencies

GnomAD3 genomes AF: 0.0000271 AC: 3 AN: 110607 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

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: 0.0000571

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000686 AC: 12 AN: 174803 AF XY: 0.0000820

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: 0.000128

Gnomad OTH exome AF: 0.000467

GnomAD4 exome AF: 0.000102 AC: 111 AN: 1091098 Hom.: 0 Cov.: 30 AF XY: 0.000117 AC XY: 42 AN XY: 357742

African (AFR) AF: 0.00 AC: 0 AN: 26163

American (AMR) AF: 0.00 AC: 0 AN: 34484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19102

East Asian (EAS) AF: 0.00 AC: 0 AN: 30065

South Asian (SAS) AF: 0.000152 AC: 8 AN: 52732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4087

European-Non Finnish (NFE) AF: 0.000120 AC: 101 AN: 838349

Other (OTH) AF: 0.0000437 AC: 2 AN: 45764

GnomAD4 genome AF: 0.0000271 AC: 3 AN: 110607 Hom.: 0 Cov.: 22 AF XY: 0.0000904 AC XY: 3 AN XY: 33181

African (AFR) AF: 0.00 AC: 0 AN: 30560

American (AMR) AF: 0.00 AC: 0 AN: 10332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2620

East Asian (EAS) AF: 0.00 AC: 0 AN: 3512

South Asian (SAS) AF: 0.00 AC: 0 AN: 2672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5947

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000571 AC: 3 AN: 52549

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.000107 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.015
DANN	Benign	0.31
DEOGEN2	Benign	0.0028	T
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-4.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.010
Sift	Benign	0.40	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.21		Loss of methylation at K228 (P = 0.0492)
MVP		0.043
MPC		0.0020
ClinPred		0.033	T
GERP RS		-5.5
Varity_R		0.023
gMVP		0.012
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs745675150; hg19: chrX-83128414;