17-41841793-C-T

Position:

• chr17-41841793-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152467.5(KLHL10):​c.195-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,613,944 control chromosomes in the GnomAD database, including 1,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (525 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (527 hom.)
• Consequence: KLHL10 NM_152467.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.788

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-41841793-C-T is Benign according to our data. Variant chr17-41841793-C-T is described in ClinVar as [Benign]. Clinvar id is 1178995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.195-30C>T		intron_variant		ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.195-30C>T		intron_variant			NP_001316524.1
KLHL10	NM_001329596.2	c.-70-30C>T		intron_variant			NP_001316525.1
KLHL10	XM_047435897.1	c.195-30C>T		intron_variant			XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.195-30C>T		intron_variant		1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.147C>T	p.Ser49Ser	synonymous_variant	2/2	4		ENSP00000416221.1
KLHL10	ENST00000448203.2	c.195-30C>T		intron_variant		4		ENSP00000391983.2
KLHL10	ENST00000485613.1	n.241-30C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6852 AN: 152112 Hom.: 524 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.0111 AC: 2761 AN: 249304 Hom.: 192 AF XY: 0.00847 AC XY: 1146 AN XY: 135334

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.00547

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000501

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00479

GnomAD4 exome AF: 0.00477 AC: 6974 AN: 1461714 Hom.: 527 Cov.: 30 AF XY: 0.00414 AC XY: 3008 AN XY: 727160

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.00653

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0451 AC: 6866 AN: 152230 Hom.: 525 Cov.: 33 AF XY: 0.0433 AC XY: 3222 AN XY: 74422

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0121 Hom.: 76

Bravo AF: 0.0514

Asia WGS AF: 0.0390 AC: 134 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs71373458; hg19: chr17-39998045;