rs2032672

chrY-19731995-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004653.5(KDM5D):c.1212+51T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0063 (0 hom., 210 hem., cov: 0)
  • Exomes 𝑓: 0.0058 (0 hom. 2076 hem.)
• Consequence: KDM5D NM_004653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00577 (2076/359697) while in subpopulation MID AF= 0.0523 (85/1624). AF 95% confidence interval is 0.0434. There are 0 homozygotes in gnomad4_exome. There are 2076 alleles in male gnomad4_exome subpopulation. Median coverage is 8. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 210 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5D	NM_004653.5	c.1212+51T>G		intron_variant		ENST00000317961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5D	ENST00000317961.9	c.1212+51T>G		intron_variant		1	NM_004653.5	P2

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 210 AN: 33189 Hom.: 0 Cov.: 0 AF XY: 0.00633 AC XY: 210 AN XY: 33189

Gnomad AFR AF: 0.00202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.000801

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.0132

GnomAD3 exomes AF: 0.00828 AC: 561 AN: 67713 Hom.: 0 AF XY: 0.00828 AC XY: 561 AN XY: 67713

Gnomad AFR exome AF: 0.000324

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0341

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00668

Gnomad FIN exome AF: 0.000178

Gnomad NFE exome AF: 0.00838

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.00577 AC: 2076 AN: 359697 Hom.: 0 Cov.: 8 AF XY: 0.00577 AC XY: 2076 AN XY: 359697

Gnomad4 AFR exome AF: 0.00484

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.0301

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00799

Gnomad4 FIN exome AF: 0.0000777

Gnomad4 NFE exome AF: 0.00445

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.00632 AC: 210 AN: 33254 Hom.: 0 Cov.: 0 AF XY: 0.00632 AC XY: 210 AN XY: 33254

Gnomad4 AFR AF: 0.00201

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.000801

Gnomad4 SAS AF: 0.00206

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00681

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0338 Hom.: 370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.5
Dann	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs2032672; hg19: chrY-21893881;