17-41841604-C-A

Position:

• chr17-41841604-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000293303.5(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 ENST00000293303.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.229

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.195-219C>A		intron_variant		ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.195-219C>A		intron_variant			NP_001316524.1
KLHL10	NM_001329596.2	c.-70-219C>A		intron_variant			NP_001316525.1
KLHL10	XM_047435897.1	c.195-219C>A		intron_variant			XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.195-219C>A		intron_variant		1	NM_152467.5	ENSP00000293303	P1
KLHL10	ENST00000438813.1	c.133-175C>A		intron_variant		4		ENSP00000416221
KLHL10	ENST00000448203.2	c.195-219C>A		intron_variant		4		ENSP00000391983
KLHL10	ENST00000485613.1	n.241-219C>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.782

Alfa AF: 0.747 Hom.: 9975

Bravo AF: 0.774

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs11079017; hg19: chr17-39997856;