X-83873538-C-G

Variant names:

• chrX-83873538-C-G
• rs971331373
• NM_021118.3:c.830C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021118.3(CYLC1):​c.830C>G​(p.Ser277Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,085,840 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S277Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: CYLC1 NM_021118.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06982246).

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.830C>G	p.Ser277Cys	missense	Exon 4 of 5	NP_066941.1	P35663
	CYLC1	NM_001271680.2		c.174+1968C>G		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.830C>G	p.Ser277Cys	missense	Exon 4 of 5	ENSP00000331556.4	P35663
	CYLC1	ENST00000621735.4	TSL:3	c.174+1968C>G		intron	N/A	ENSP00000480907.1	A0A087WXC8

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.21e-7 AC: 1 AN: 1085840 Hom.: 0 Cov.: 29 AF XY: 0.00000283 AC XY: 1 AN XY: 353254

African (AFR) AF: 0.00 AC: 0 AN: 25936

American (AMR) AF: 0.00 AC: 0 AN: 34126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18965

East Asian (EAS) AF: 0.00 AC: 0 AN: 30067

South Asian (SAS) AF: 0.00 AC: 0 AN: 52283

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40367

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 834481

Other (OTH) AF: 0.00 AC: 0 AN: 45561

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.0048	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.055
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.030
Sift	Benign	0.032	D
Sift4G	Benign	0.067	T
Vest4		0.16
MutPred		0.40		Gain of helix (P = 0.0225)
MVP		0.043
MPC		0.0021
ClinPred		0.13	T
Varity_R		0.16
gMVP		0.0042
Mutation Taster		=97/3	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: rs971331373; hg19: chrX-83128546;