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

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152467.5(KLHL10):​c.195-219C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,094 control chromosomes in the GnomAD database, including 44,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44028 hom., cov: 32)
• Consequence: KLHL10 NM_152467.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 17-41841604-C-A is Benign according to our data. Variant chr17-41841604-C-A is described in ClinVar as [Benign]. Clinvar id is 1252409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.195-219C>A		intron_variant	Intron 1 of 4	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.195-219C>A		intron_variant	Intron 3 of 6		NP_001316524.1
KLHL10	NM_001329596.2	c.-70-219C>A		intron_variant	Intron 1 of 4		NP_001316525.1
KLHL10	XM_047435897.1	c.195-219C>A		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>A		intron_variant	Intron 1 of 4	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.133-175C>A		intron_variant	Intron 1 of 1	4		ENSP00000416221.1
KLHL10	ENST00000448203.2	c.195-219C>A		intron_variant	Intron 3 of 3	4		ENSP00000391983.2
KLHL10	ENST00000485613.1	n.241-219C>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115299 AN: 151976 Hom.: 43997 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.759 AC: 115375 AN: 152094 Hom.: 44028 Cov.: 32 AF XY: 0.756 AC XY: 56234 AN XY: 74362

African (AFR) AF: 0.727 AC: 30154 AN: 41498

American (AMR) AF: 0.845 AC: 12908 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3019 AN: 3472

East Asian (EAS) AF: 0.824 AC: 4250 AN: 5160

South Asian (SAS) AF: 0.827 AC: 3986 AN: 4820

European-Finnish (FIN) AF: 0.627 AC: 6629 AN: 10566

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51790 AN: 67992

Other (OTH) AF: 0.782 AC: 1648 AN: 2108

Alfa AF: 0.749 Hom.: 13488

Bravo AF: 0.774

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.47
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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;