chr6-4943770-T-TAAAAAA

Variant names:

• chr6-4943770-T-TAAAAAA
• rs34649909
• NM_004824.4:c.1332+26_1332+31dupAAAAAA

Variant summary

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

The NM_004824.4(CDYL):​c.1332+26_1332+31dupAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: CDYL NM_004824.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDYL	NM_004824.4	c.1332+26_1332+31dupAAAAAA		intron_variant	Intron 5 of 6	ENST00000397588.8	NP_004815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDYL	ENST00000397588.8	c.1332+26_1332+31dupAAAAAA		intron_variant	Intron 5 of 6	1	NM_004824.4	ENSP00000380718.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000253 AC: 26 AN: 1029062 Hom.: 0 Cov.: 17 AF XY: 0.0000233 AC XY: 12 AN XY: 515252

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000812 AC: 2 AN: 24622

American (AMR) AF: 0.00 AC: 0 AN: 25994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18562

East Asian (EAS) AF: 0.00 AC: 0 AN: 34504

South Asian (SAS) AF: 0.0000333 AC: 2 AN: 60028

European-Finnish (FIN) AF: 0.0000242 AC: 1 AN: 41258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2960

European-Non Finnish (NFE) AF: 0.0000257 AC: 20 AN: 777066

Other (OTH) AF: 0.0000227 AC: 1 AN: 44068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34649909; hg19: chr6-4944004;