X-83873530-G-A

Variant names:

• chrX-83873530-G-A
• rs148140928
• NM_021118.3:c.822G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP7 BS2_Supporting

The NM_021118.3(CYLC1):​c.822G>A​(p.Lys274Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000644 in 1,086,792 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 4 hem.)
• Consequence: CYLC1 NM_021118.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.
• 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.822G>A	p.Lys274Lys	synonymous	Exon 4 of 5	NP_066941.1	P35663
	CYLC1	NM_001271680.2		c.174+1960G>A		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.822G>A	p.Lys274Lys	synonymous	Exon 4 of 5	ENSP00000331556.4	P35663
	CYLC1	ENST00000621735.4	TSL:3	c.174+1960G>A		intron	N/A	ENSP00000480907.1	A0A087WXC8

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000644 AC: 7 AN: 1086792 Hom.: 0 Cov.: 29 AF XY: 0.0000113 AC XY: 4 AN XY: 354080

African (AFR) AF: 0.00 AC: 0 AN: 25996

American (AMR) AF: 0.00 AC: 0 AN: 34286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19037

East Asian (EAS) AF: 0.00 AC: 0 AN: 30063

South Asian (SAS) AF: 0.00 AC: 0 AN: 52530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40373

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4065

European-Non Finnish (NFE) AF: 0.00000839 AC: 7 AN: 834811

Other (OTH) AF: 0.00 AC: 0 AN: 45631

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		1.7

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: rs148140928; hg19: chrX-83128538; COSMIC: COSV100255030;