17-41841889-C-G

Variant names:

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

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>G​(p.Pro87Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P87P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL10 NM_152467.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 26 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=-0.65).
• 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>G	p.Pro87Pro	synonymous	Exon 2 of 5	NP_689680.2	A0A140VJM8
	KLHL10	NM_001329595.1		c.261C>G	p.Pro87Pro	synonymous	Exon 4 of 7	NP_001316524.1	A0A140VJM8
	KLHL10	NM_001329596.2		c.-4C>G		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>G	p.Pro87Pro	synonymous	Exon 2 of 5	ENSP00000293303.4	Q6JEL2
	KLHL10	ENST00000859834.1		c.261C>G	p.Pro87Pro	synonymous	Exon 4 of 7	ENSP00000529893.1
	KLHL10	ENST00000913027.1		c.261C>G	p.Pro87Pro	synonymous	Exon 4 of 7	ENSP00000583086.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.92
DANN	Benign	0.66
PhyloP100		-3.3

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

Other links and lift over

dbSNP: rs1529933; hg19: chr17-39998141;