6-4943770-TAAAAAAAA-TAAAAAAAAAAA

Variant names:

• chr6-4943770-T-TAAA
• rs34649909
• NM_004824.4:c.1332+29_1332+31dupAAA

Variant summary

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

The NM_004824.4(CDYL):​c.1332+29_1332+31dupAAA 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 0.11 (961 hom., cov: 0)
  • Exomes 𝑓: 0.088 (485 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 (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004824.4. 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
	CDYL	NM_004824.4	MANE Select	c.1332+29_1332+31dupAAA		intron	N/A	NP_004815.3
	CDYL	NM_001368125.1		c.1494+29_1494+31dupAAA		intron	N/A	NP_001355054.1	Q9Y232-1
	CDYL	NM_001368126.1		c.1266+29_1266+31dupAAA		intron	N/A	NP_001355055.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL	ENST00000397588.8	TSL:1 MANE Select	c.1332+29_1332+31dupAAA		intron	N/A	ENSP00000380718.3	Q9Y232-2
	CDYL	ENST00000328908.9	TSL:1	c.1494+29_1494+31dupAAA		intron	N/A	ENSP00000330512.5	Q9Y232-1
	CDYL	ENST00000343762.5	TSL:1	c.936+29_936+31dupAAA		intron	N/A	ENSP00000340908.5	Q9Y232-4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 15795 AN: 144126 Hom.: 960 Cov.: 0

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.0731

Gnomad EAS AF: 0.0107

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0911

GnomAD2 exomes AF: 0.0555 AC: 7870 AN: 141918 AF XY: 0.0549

Gnomad AFR exome AF: 0.0667

Gnomad AMR exome AF: 0.0276

Gnomad ASJ exome AF: 0.0347

Gnomad EAS exome AF: 0.00945

Gnomad FIN exome AF: 0.0848

Gnomad NFE exome AF: 0.0685

Gnomad OTH exome AF: 0.0651

GnomAD4 exome AF: 0.0879 AC: 88714 AN: 1009768 Hom.: 485 Cov.: 17 AF XY: 0.0858 AC XY: 43387 AN XY: 505540

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

African (AFR) AF: 0.0829 AC: 1995 AN: 24070

American (AMR) AF: 0.0330 AC: 846 AN: 25638

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 864 AN: 18252

East Asian (EAS) AF: 0.00693 AC: 238 AN: 34336

South Asian (SAS) AF: 0.0442 AC: 2617 AN: 59216

European-Finnish (FIN) AF: 0.0984 AC: 3954 AN: 40192

Middle Eastern (MID) AF: 0.0367 AC: 107 AN: 2914

European-Non Finnish (NFE) AF: 0.0980 AC: 74689 AN: 761980

Other (OTH) AF: 0.0789 AC: 3404 AN: 43170

⚠️ 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: 0.110 AC: 15810 AN: 144160 Hom.: 961 Cov.: 0 AF XY: 0.107 AC XY: 7481 AN XY: 69646

African (AFR) AF: 0.112 AC: 4371 AN: 39024

American (AMR) AF: 0.0680 AC: 991 AN: 14570

Ashkenazi Jewish (ASJ) AF: 0.0731 AC: 250 AN: 3422

East Asian (EAS) AF: 0.0110 AC: 54 AN: 4930

South Asian (SAS) AF: 0.0646 AC: 292 AN: 4518

European-Finnish (FIN) AF: 0.136 AC: 1113 AN: 8186

Middle Eastern (MID) AF: 0.0321 AC: 9 AN: 280

European-Non Finnish (NFE) AF: 0.127 AC: 8414 AN: 66344

Other (OTH) AF: 0.0932 AC: 185 AN: 1986

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34649909; hg19: chr6-4944004;