17-41841793-C-T

Variant names:

• chr17-41841793-C-T
• rs71373458
• NM_152467.5:c.195-30C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.195-30C>T		intron_variant	Intron 1 of 4	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.195-30C>T		intron_variant	Intron 3 of 6		NP_001316524.1
KLHL10	NM_001329596.2	c.-70-30C>T		intron_variant	Intron 1 of 4		NP_001316525.1
KLHL10	XM_047435897.1	c.195-30C>T		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.195-30C>T		intron_variant	Intron 1 of 4	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.147C>T	p.Ser49Ser	synonymous_variant	Exon 2 of 2	4		ENSP00000416221.1
KLHL10	ENST00000448203.2	c.195-30C>T		intron_variant	Intron 3 of 3	4		ENSP00000391983.2
KLHL10	ENST00000485613.1	n.241-30C>T		intron_variant	Intron 1 of 1	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

GnomAD2 exomes AF: 0.0111 AC: 2761 AN: 249304 AF XY: 0.00847

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 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

African (AFR) AF: 0.169 AC: 5654 AN: 33464

American (AMR) AF: 0.00653 AC: 292 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.00151 AC: 130 AN: 86154

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53400

Middle Eastern (MID) AF: 0.00538 AC: 31 AN: 5764

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1111976

Other (OTH) AF: 0.0112 AC: 679 AN: 60396

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

African (AFR) AF: 0.157 AC: 6519 AN: 41514

American (AMR) AF: 0.0149 AC: 227 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68020

Other (OTH) AF: 0.0326 AC: 69 AN: 2116

Alfa AF: 0.0146 Hom.: 112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

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	-0.89
CADD	Benign	5.7
DANN	Benign	0.55
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71373458; hg19: chr17-39998045;