NM_152467.5:c.685-259G>A

Variant names:

• chr17-41844867-G-A
• rs60090576
• NM_152467.5:c.685-259G>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.685-259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,622 control chromosomes in the GnomAD database, including 11,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11468 hom., cov: 31)
• Consequence: KLHL10 NM_152467.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.128
• Publications: 3 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=-0.89).
• BP6: Variant 17-41844867-G-A is Benign according to our data. Variant chr17-41844867-G-A is described in ClinVar as [Benign]. Clinvar id is 1254282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.685-259G>A		intron_variant	Intron 2 of 4	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.685-259G>A		intron_variant	Intron 4 of 6		NP_001316524.1
KLHL10	NM_001329596.2	c.421-259G>A		intron_variant	Intron 2 of 4		NP_001316525.1
KLHL10	XM_047435897.1	c.685-259G>A		intron_variant	Intron 3 of 5		XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.685-259G>A		intron_variant	Intron 2 of 4	1	NM_152467.5	ENSP00000293303.4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56914 AN: 151504 Hom.: 11467 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.375 AC: 56914 AN: 151622 Hom.: 11468 Cov.: 31 AF XY: 0.375 AC XY: 27742 AN XY: 74054

African (AFR) AF: 0.235 AC: 9735 AN: 41340

American (AMR) AF: 0.393 AC: 5972 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2057 AN: 3466

East Asian (EAS) AF: 0.504 AC: 2587 AN: 5132

South Asian (SAS) AF: 0.530 AC: 2540 AN: 4794

European-Finnish (FIN) AF: 0.308 AC: 3235 AN: 10492

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29371 AN: 67880

Other (OTH) AF: 0.401 AC: 842 AN: 2102

Alfa AF: 0.400 Hom.: 1545

Bravo AF: 0.370

Asia WGS AF: 0.467 AC: 1623 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.85
PhyloP100		0.13
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: rs60090576; hg19: chr17-40001119;