chr6-4943770-TAA-T

Variant names:

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

Variant summary

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

The NM_004824.4(CDYL):​c.1332+30_1332+31delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00813 in 1,170,092 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0092 (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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL	NM_004824.4	MANE Select	c.1332+30_1332+31delAA		intron	N/A	NP_004815.3
	CDYL	NM_001368125.1		c.1494+30_1494+31delAA		intron	N/A	NP_001355054.1
	CDYL	NM_001368126.1		c.1266+30_1266+31delAA		intron	N/A	NP_001355055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL	ENST00000397588.8	TSL:1 MANE Select	c.1332+30_1332+31delAA		intron	N/A	ENSP00000380718.3
	CDYL	ENST00000328908.9	TSL:1	c.1494+30_1494+31delAA		intron	N/A	ENSP00000330512.5
	CDYL	ENST00000343762.5	TSL:1	c.936+30_936+31delAA		intron	N/A	ENSP00000340908.5

Frequencies

GnomAD3 genomes AF: 0.000215 AC: 31 AN: 144306 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000274

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000440

Gnomad FIN AF: 0.000851

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000211

Gnomad OTH AF: 0.00101

GnomAD2 exomes AF: 0.0181 AC: 2571 AN: 141918 AF XY: 0.0186

Gnomad AFR exome AF: 0.00665

Gnomad AMR exome AF: 0.00983

Gnomad ASJ exome AF: 0.0174

Gnomad EAS exome AF: 0.0121

Gnomad FIN exome AF: 0.0245

Gnomad NFE exome AF: 0.0199

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.00925 AC: 9485 AN: 1025754 Hom.: 0 AF XY: 0.00951 AC XY: 4886 AN XY: 513556

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

African (AFR) AF: 0.00306 AC: 75 AN: 24472

American (AMR) AF: 0.00770 AC: 199 AN: 25848

Ashkenazi Jewish (ASJ) AF: 0.00665 AC: 123 AN: 18488

East Asian (EAS) AF: 0.00553 AC: 190 AN: 34386

South Asian (SAS) AF: 0.0164 AC: 980 AN: 59760

European-Finnish (FIN) AF: 0.0164 AC: 673 AN: 41060

Middle Eastern (MID) AF: 0.00982 AC: 29 AN: 2952

European-Non Finnish (NFE) AF: 0.00880 AC: 6816 AN: 774886

Other (OTH) AF: 0.00911 AC: 400 AN: 43902

⚠️ 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: 0.000215 AC: 31 AN: 144338 Hom.: 0 Cov.: 0 AF XY: 0.000215 AC XY: 15 AN XY: 69742

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

African (AFR) AF: 0.0000512 AC: 2 AN: 39082

American (AMR) AF: 0.000274 AC: 4 AN: 14586

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4932

South Asian (SAS) AF: 0.000442 AC: 2 AN: 4526

European-Finnish (FIN) AF: 0.000851 AC: 7 AN: 8230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000211 AC: 14 AN: 66390

Other (OTH) AF: 0.00101 AC: 2 AN: 1990

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000173224), which strongly suggests a high chance of mosaicism in these individuals.

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

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

Other links and lift over

dbSNP: rs34649909; hg19: chr6-4944004;