rs2032629

chrY-19703935-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BS1 BS2

The NM_004653.5(KDM5D):c.*2060C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 33,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (0 hom., 157 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KDM5D NM_004653.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

Genes affected

KDM5D (HGNC:11115): (lysine demethylase 5D) This gene encodes a protein containing zinc finger domains. A short peptide derived from this protein is a minor histocompatibility antigen which can lead to graft rejection of male donor cells in a female recipient. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00467 (157/33654) while in subpopulation AMR AF= 0.0208 (78/3749). AF 95% confidence interval is 0.0171. There are 0 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 157 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5D	NM_004653.5	c.*2060C>T		3_prime_UTR_variant	27/27	ENST00000317961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5D	ENST00000317961.9	c.*2060C>T		3_prime_UTR_variant	27/27	1	NM_004653.5	P2
KDM5D	ENST00000469599.6	n.5431C>T		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 157 AN: 33592 Hom.: 0 Cov.: 0 AF XY: 0.00467 AC XY: 157 AN XY: 33592

Gnomad AFR AF: 0.00151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.00390

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00420

Gnomad OTH AF: 0.0127

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00467 AC: 157 AN: 33654 Hom.: 0 Cov.: 0 AF XY: 0.00467 AC XY: 157 AN XY: 33654

Gnomad4 AFR AF: 0.00150

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.00390

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00420

Gnomad4 OTH AF: 0.0126

Alfa AF: 0.0126 Hom.: 290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.5
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2032629; hg19: chrY-21865821;