6-4943770-TAAAAAAAA-TAAAAAAAAAAAAA

Variant names:

• chr6-4943770-T-TAAAAA
• rs34649909
• NM_004824.4:c.1332+27_1332+31dupAAAAA

Variant summary

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

The NM_004824.4(CDYL):​c.1332+27_1332+31dupAAAAA 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: 𝑓 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00033 (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+27_1332+31dupAAAAA		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+27_1332+31dupAAAAA		intron_variant	Intron 5 of 6	1	NM_004824.4	ENSP00000380718.3

Frequencies

GnomAD3 genomes AF: 0.00000693 AC: 1 AN: 144314 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000333 AC: 342 AN: 1028480 Hom.: 0 Cov.: 17 AF XY: 0.000338 AC XY: 174 AN XY: 514982

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

African (AFR) AF: 0.000406 AC: 10 AN: 24602

American (AMR) AF: 0.000231 AC: 6 AN: 25990

Ashkenazi Jewish (ASJ) AF: 0.000162 AC: 3 AN: 18560

East Asian (EAS) AF: 0.0000290 AC: 1 AN: 34502

South Asian (SAS) AF: 0.000533 AC: 32 AN: 59992

European-Finnish (FIN) AF: 0.000243 AC: 10 AN: 41234

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

European-Non Finnish (NFE) AF: 0.000350 AC: 272 AN: 776584

Other (OTH) AF: 0.000182 AC: 8 AN: 44056

⚠️ 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 AF: 0.00000693 AC: 1 AN: 144314 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 69688

African (AFR) AF: 0.00 AC: 0 AN: 39002

American (AMR) AF: 0.00 AC: 0 AN: 14578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 4544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66402

Other (OTH) AF: 0.00 AC: 0 AN: 1980

Alfa AF: 0.00 Hom.: 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;