NM_004653.5:c.2031+92_2031+93insA

Variant names:

• chrY-19716186-G-GT
• rs2032623
• NM_004653.5:c.2031+92_2031+93insA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004653.5(KDM5D):​c.2031+92_2031+93insA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0058 (0 hom., 200 hem., cov: 0)
  • Exomes 𝑓: 0.00065 (0 hom. 149 hem.)
• Consequence: KDM5D NM_004653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 6 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00583 (200/34293) while in subpopulation AFR AF = 0.0217 (191/8814). AF 95% confidence interval is 0.0192. There are 0 homozygotes in GnomAd4. There are 200 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 200 gene

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.2031+92_2031+93insA		intron	N/A	NP_004644.2
	KDM5D	NM_001146705.2		c.2124+92_2124+93insA		intron	N/A	NP_001140177.1	Q9BY66-3
	KDM5D	NM_001146706.2		c.1860+92_1860+93insA		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.2031+92_2031+93insA		intron	N/A	ENSP00000322408.4	Q9BY66-1
	KDM5D	ENST00000541639.5	TSL:1	c.2124+92_2124+93insA		intron	N/A	ENSP00000444293.1	Q9BY66-3
	KDM5D	ENST00000382806.6	TSL:1	c.1860+92_1860+93insA		intron	N/A	ENSP00000372256.2	Q9BY66-2

Frequencies

GnomAD3 genomes AF: 0.00549 AC: 188 AN: 34231 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000646

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00210

GnomAD4 exome AF: 0.000655 AC: 149 AN: 227644 Hom.: 0 Cov.: 0 AF XY: 0.000655 AC XY: 149 AN XY: 227644

African (AFR) AF: 0.0243 AC: 116 AN: 4782

American (AMR) AF: 0.000999 AC: 9 AN: 9010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5598

East Asian (EAS) AF: 0.00 AC: 0 AN: 9012

South Asian (SAS) AF: 0.0000721 AC: 2 AN: 27750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12317

Middle Eastern (MID) AF: 0.00159 AC: 2 AN: 1261

European-Non Finnish (NFE) AF: 0.0000338 AC: 5 AN: 147965

Other (OTH) AF: 0.00151 AC: 15 AN: 9949

GnomAD4 genome AF: 0.00583 AC: 200 AN: 34293 Hom.: 0 Cov.: 0 AF XY: 0.00583 AC XY: 200 AN XY: 34293

African (AFR) AF: 0.0217 AC: 191 AN: 8814

American (AMR) AF: 0.00182 AC: 7 AN: 3839

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 778

East Asian (EAS) AF: 0.00 AC: 0 AN: 1280

South Asian (SAS) AF: 0.000644 AC: 1 AN: 1552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 13719

Other (OTH) AF: 0.00208 AC: 1 AN: 480

Alfa AF: 0.000357 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2032623; hg19: chrY-21878072;