6-4943770-TAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr6-4943770-T-TAA
• rs34649909
• NM_004824.4:c.1332+30_1332+31dupAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004824.4(CDYL):​c.1332+30_1332+31dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.092 (665 hom., cov: 0)
  • Exomes 𝑓: 0.12 (210 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDYL	NM_004824.4	c.1332+30_1332+31dupAA		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+30_1332+31dupAA		intron_variant	Intron 5 of 6	1	NM_004824.4	ENSP00000380718.3

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 13340 AN: 144264 Hom.: 668 Cov.: 0

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0972

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.0863

GnomAD2 exomes AF: 0.0842 AC: 11951 AN: 141918 AF XY: 0.0820

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0537

Gnomad ASJ exome AF: 0.0975

Gnomad EAS exome AF: 0.0706

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0895

Gnomad OTH exome AF: 0.0961

GnomAD4 exome AF: 0.121 AC: 122684 AN: 1016214 Hom.: 210 Cov.: 17 AF XY: 0.119 AC XY: 60438 AN XY: 508788

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

African (AFR) AF: 0.110 AC: 2673 AN: 24202

American (AMR) AF: 0.0635 AC: 1630 AN: 25650

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2168 AN: 18222

East Asian (EAS) AF: 0.0841 AC: 2852 AN: 33908

South Asian (SAS) AF: 0.0913 AC: 5413 AN: 59320

European-Finnish (FIN) AF: 0.112 AC: 4530 AN: 40550

Middle Eastern (MID) AF: 0.111 AC: 325 AN: 2932

European-Non Finnish (NFE) AF: 0.128 AC: 98010 AN: 767950

Other (OTH) AF: 0.117 AC: 5083 AN: 43480

⚠️ 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: 0.0924 AC: 13336 AN: 144292 Hom.: 665 Cov.: 0 AF XY: 0.0923 AC XY: 6435 AN XY: 69710

African (AFR) AF: 0.119 AC: 4648 AN: 39048

American (AMR) AF: 0.0583 AC: 851 AN: 14588

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 330 AN: 3422

East Asian (EAS) AF: 0.0687 AC: 339 AN: 4932

South Asian (SAS) AF: 0.0553 AC: 250 AN: 4522

European-Finnish (FIN) AF: 0.0972 AC: 800 AN: 8230

Middle Eastern (MID) AF: 0.0755 AC: 21 AN: 278

European-Non Finnish (NFE) AF: 0.0856 AC: 5679 AN: 66380

Other (OTH) AF: 0.0853 AC: 170 AN: 1992

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
Mutation Taster		=100/0	polymorphism (auto)

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;