rs2032640

chrY-19730686-C-T

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.1371+1086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 30,137 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 0.0065 (0 hom., 197 hem., cov: 0)
• Consequence: KDM5D NM_004653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.92).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00654 (197/30137) while in subpopulation AMR AF= 0.034 (122/3593). AF 95% confidence interval is 0.0291. There are 0 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 196 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5D	NM_004653.5	c.1371+1086G>A		intron_variant		ENST00000317961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5D	ENST00000317961.9	c.1371+1086G>A		intron_variant		1	NM_004653.5	P2

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 196 AN: 30075 Hom.: 0 Cov.: 0 AF XY: 0.00652 AC XY: 196 AN XY: 30075

Gnomad AFR AF: 0.00201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.0176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00654 AC: 197 AN: 30137 Hom.: 0 Cov.: 0 AF XY: 0.00654 AC XY: 197 AN XY: 30137

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00178

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0151 Hom.: 232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.9
Dann	Benign	0.56

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: rs2032640; hg19: chrY-21892572;