rs2032673

Variant names:

• chrY-19732172-T-C
• rs2032673
• NM_004653.5:c.1093-7A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004653.5(KDM5D):​c.1093-7A>G variant causes a splice region, 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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, intron
• Scores: Splicing: ADA: 0.00004107
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004653.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5D	NM_004653.5	MANE Select	c.1093-7A>G		splice_region intron	N/A	NP_004644.2
	KDM5D	NM_001146705.2		c.1093-7A>G		splice_region intron	N/A	NP_001140177.1	Q9BY66-3
	KDM5D	NM_001146706.2		c.922-7A>G		splice_region intron	N/A	NP_001140178.1	Q9BY66-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5D	ENST00000317961.9	TSL:1 MANE Select	c.1093-7A>G		splice_region intron	N/A	ENSP00000322408.4	Q9BY66-1
	KDM5D	ENST00000541639.5	TSL:1	c.1093-7A>G		splice_region intron	N/A	ENSP00000444293.1	Q9BY66-3
	KDM5D	ENST00000382806.6	TSL:1	c.922-7A>G		splice_region intron	N/A	ENSP00000372256.2	Q9BY66-2

Frequencies

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

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

GnomAD2 exomes AF: 0.0265 AC: 1512 AN: 57102 AF XY: 0.0265

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 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

African (AFR) AF: 0.000719 AC: 5 AN: 6958

American (AMR) AF: 0.000547 AC: 5 AN: 9134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6650

East Asian (EAS) AF: 0.000107 AC: 1 AN: 9374

South Asian (SAS) AF: 0.137 AC: 4296 AN: 31321

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12551

Middle Eastern (MID) AF: 0.00434 AC: 7 AN: 1613

European-Non Finnish (NFE) AF: 0.000731 AC: 193 AN: 264177

Other (OTH) AF: 0.0136 AC: 191 AN: 14038

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

African (AFR) AF: 0.000241 AC: 2 AN: 8283

American (AMR) AF: 0.000280 AC: 1 AN: 3571

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 755

East Asian (EAS) AF: 0.00 AC: 0 AN: 1212

South Asian (SAS) AF: 0.151 AC: 209 AN: 1384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 75

European-Non Finnish (NFE) AF: 0.000301 AC: 4 AN: 13273

Other (OTH) AF: 0.00224 AC: 1 AN: 446

Alfa AF: 0.0900 Hom.: 4305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.38
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2032673; hg19: chrY-21894058;