17-41837519-G-A

Position:

• chr17-41837519-G-A

Variant summary

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

The NM_001329595.1(KLHL10):​c.-76G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,003,510 control chromosomes in the GnomAD database, including 290,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (44923 hom., cov: 33)
  • Exomes 𝑓: 0.76 (245889 hom.)
• Consequence: KLHL10 NM_001329595.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 17-41837519-G-A is Benign according to our data. Variant chr17-41837519-G-A is described in ClinVar as [Benign]. Clinvar id is 1238553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL10	NM_001329595.1	c.-76G>A		5_prime_UTR_variant	2/7		NP_001316524.1
KLHL10	XM_047435897.1	c.-76G>A		5_prime_UTR_variant	1/6		XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000448203.2	c.-76G>A		5_prime_UTR_variant	2/4	4		ENSP00000391983

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116455 AN: 151978 Hom.: 44887 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.759 AC: 645805 AN: 851414 Hom.: 245889 Cov.: 20 AF XY: 0.758 AC XY: 299709 AN XY: 395164

Gnomad4 AFR exome AF: 0.748

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 0.834

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.754

Gnomad4 OTH exome AF: 0.776

GnomAD4 genome AF: 0.766 AC: 116540 AN: 152096 Hom.: 44923 Cov.: 33 AF XY: 0.764 AC XY: 56815 AN XY: 74342

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.784

Alfa AF: 0.776 Hom.: 59581

Bravo AF: 0.782

Asia WGS AF: 0.827 AC: 2876 AN: 3478

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4796715; hg19: chr17-39993771;