17-41844867-G-A

Position:

• chr17-41844867-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.685-259G>A		intron_variant		ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.685-259G>A		intron_variant			NP_001316524.1
KLHL10	NM_001329596.2	c.421-259G>A		intron_variant			NP_001316525.1
KLHL10	XM_047435897.1	c.685-259G>A		intron_variant			XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.685-259G>A		intron_variant		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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.401

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

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	-0.89
CADD	Benign	3.4
DANN	Benign	0.85

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: rs60090576; hg19: chr17-40001119;