X-83873149-A-G

Variant names:

• chrX-83873149-A-G
• rs145042237
• NM_021118.3:c.441A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_021118.3(CYLC1):​c.441A>G​(p.Ile147Met) 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 1,088,237 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I147I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 2 hem.)
• Consequence: CYLC1 NM_021118.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• 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 -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10053894).
• 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.441A>G	p.Ile147Met	missense	Exon 4 of 5	NP_066941.1	P35663
	CYLC1	NM_001271680.2		c.174+1579A>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.441A>G	p.Ile147Met	missense	Exon 4 of 5	ENSP00000331556.4	P35663
	CYLC1	ENST00000621735.4	TSL:3	c.174+1579A>G		intron	N/A	ENSP00000480907.1	A0A087WXC8

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000643 AC: 7 AN: 1088237 Hom.: 0 Cov.: 30 AF XY: 0.00000562 AC XY: 2 AN XY: 355727

African (AFR) AF: 0.00 AC: 0 AN: 25891

American (AMR) AF: 0.00 AC: 0 AN: 33887

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19024

East Asian (EAS) AF: 0.00 AC: 0 AN: 30080

South Asian (SAS) AF: 0.00 AC: 0 AN: 52184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40315

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4076

European-Non Finnish (NFE) AF: 0.00000836 AC: 7 AN: 837154

Other (OTH) AF: 0.00 AC: 0 AN: 45626

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.50
DEOGEN2	Benign	0.0027	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.11
Sift	Benign	0.26	T
Sift4G	Benign	0.35	T
Polyphen		0.32	B
Vest4		0.040
MutPred		0.13		Gain of MoRF binding (P = 0.0868)
MVP		0.40
MPC		0.0026
ClinPred		0.28	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.0091
Mutation Taster		=96/4	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: rs145042237; hg19: chrX-83128157;