NM_152467.5:c.195-219C>G

Variant names:

• chr17-41841604-C-G
• rs11079017
• NM_152467.5:c.195-219C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152467.5(KLHL10):​c.195-219C>G variant causes a intron 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL10 NM_152467.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 5 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.195-219C>G		intron_variant	Intron 1 of 4	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.195-219C>G		intron_variant	Intron 3 of 6		NP_001316524.1
KLHL10	NM_001329596.2	c.-70-219C>G		intron_variant	Intron 1 of 4		NP_001316525.1
KLHL10	XM_047435897.1	c.195-219C>G		intron_variant	Intron 2 of 5		XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.195-219C>G		intron_variant	Intron 1 of 4	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.133-175C>G		intron_variant	Intron 1 of 1	4		ENSP00000416221.1
KLHL10	ENST00000448203.2	c.195-219C>G		intron_variant	Intron 3 of 3	4		ENSP00000391983.2
KLHL10	ENST00000485613.1	n.241-219C>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.45
PhyloP100		-0.23

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: rs11079017; hg19: chr17-39997856;