rs1529933

Variant names:

• chr17-41841889-C-A
• rs1529933
• NM_152467.5:c.261C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41841889-C-A
• chr17-41841889-C-G
• chr17-41841889-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152467.5(KLHL10):​c.261C>A​(p.Pro87Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. P87P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLHL10 NM_152467.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 0 publications found

Genes affected

KLHL10 (HGNC:18829): (kelch like family member 10) The protein encoded by this gene belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain a BACK domain and six C-terminal kelch repeats. Kelch domains are thought to form a four stranded beta-sheet blade structure that can fold into a beta-propeller domain when multiple kelch repeats are found together. Mutations in this gene have been associated with oligozoospermia in some infertile males. [provided by RefSeq, Jul 2016]

KLHL10 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 11

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152467.5. 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
	KLHL10	NM_152467.5	MANE Select	c.261C>A	p.Pro87Pro	synonymous	Exon 2 of 5	NP_689680.2	A0A140VJM8
	KLHL10	NM_001329595.1		c.261C>A	p.Pro87Pro	synonymous	Exon 4 of 7	NP_001316524.1	A0A140VJM8
	KLHL10	NM_001329596.2		c.-4C>A		5_prime_UTR	Exon 2 of 5	NP_001316525.1	B4DX37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL10	ENST00000293303.5	TSL:1 MANE Select	c.261C>A	p.Pro87Pro	synonymous	Exon 2 of 5	ENSP00000293303.4	Q6JEL2
	KLHL10	ENST00000859834.1		c.261C>A	p.Pro87Pro	synonymous	Exon 4 of 7	ENSP00000529893.1
	KLHL10	ENST00000913027.1		c.261C>A	p.Pro87Pro	synonymous	Exon 4 of 7	ENSP00000583086.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 58 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-3.3

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1529933; hg19: chr17-39998141;