rs2032673

chrY-19732172-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004653.5(KDM5D):c.1093-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (0 hom., 217 hem., cov: 0)
  • Exomes 𝑓: 0.013 (0 hom. 4698 hem.)
• Consequence: KDM5D NM_004653.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004107
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant Y-19732172-T-C is Benign according to our data. Variant chrY-19732172-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5D	NM_004653.5	c.1093-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000317961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5D	ENST00000317961.9	c.1093-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004653.5	P2

Frequencies

GnomAD3 genomes AF: 0.00660 AC: 214 AN: 32409 Hom.: 0 Cov.: 0 AF XY: 0.00660 AC XY: 214 AN XY: 32409

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.00226

GnomAD3 exomes AF: 0.0265 AC: 1512 AN: 57102 Hom.: 0 AF XY: 0.0265 AC XY: 1512 AN XY: 57102

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.000624

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000251

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.000197

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.0129

GnomAD4 exome AF: 0.0132 AC: 4698 AN: 355816 Hom.: 0 Cov.: 1 AF XY: 0.0132 AC XY: 4698 AN XY: 355816

Gnomad4 AFR exome AF: 0.000719

Gnomad4 AMR exome AF: 0.000547

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000731

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.00668 AC: 217 AN: 32473 Hom.: 0 Cov.: 0 AF XY: 0.00668 AC XY: 217 AN XY: 32473

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000280

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000301

Gnomad4 OTH AF: 0.00224

Alfa AF: 0.117 Hom.: 4223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.020		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: rs2032673; hg19: chrY-21894058;