6-4935564-A-G

Position:

• chr6-4935564-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004824.4(CDYL):​c.741A>G​(p.Ile247Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDYL NM_004824.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.641

Genes affected

CDYL (HGNC:1811): (chromodomain Y like) Chromodomain Y is a primate-specific Y-chromosomal gene family expressed exclusively in the testis and implicated in infertility. Although the Y-linked genes are testis-specific, this autosomal gene is ubiquitously expressed. The Y-linked genes arose by retrotransposition of an mRNA from this gene, followed by amplification of the retroposed gene. Proteins encoded by this gene superfamily possess a chromodomain, a motif implicated in chromatin binding and gene suppression, and a catalytic domain believed to be involved in histone acetylation. Multiple proteins are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

CDYL (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08480644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDYL	NM_004824.4	c.741A>G	p.Ile247Met	missense_variant	3/7	ENST00000397588.8	NP_004815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL	ENST00000397588.8	c.741A>G	p.Ile247Met	missense_variant	3/7	1	NM_004824.4	ENSP00000380718.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.741A>G (p.I247M) alteration is located in exon 3 (coding exon 3) of the CDYL gene. This alteration results from a A to G substitution at nucleotide position 741, causing the isoleucine (I) at amino acid position 247 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.027	T;T;.;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.43	T;T;T;.;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.085	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.38	N;N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.27	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.0090	B;.;B;.;.
Vest4		0.18
MutPred		0.46		Gain of disorder (P = 0.022);.;.;.;.;
MVP		0.40
MPC		0.25
ClinPred		0.16	T
GERP RS		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs1758166049; hg19: chr6-4935798;