chr17-41837519-G-C

Variant names:

• chr17-41837519-G-C
• rs4796715
• NM_001329595.1:c.-76G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001329595.1(KLHL10):​c.-76G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLHL10 NM_001329595.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 19 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_001329595.1	c.-76G>C		5_prime_UTR_variant	Exon 2 of 7		NP_001316524.1
KLHL10	XM_047435897.1	c.-76G>C		5_prime_UTR_variant	Exon 1 of 6		XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000448203.2	c.-76G>C		5_prime_UTR_variant	Exon 2 of 4	4		ENSP00000391983.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 858836 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 398502

African (AFR) AF: 0.00 AC: 0 AN: 16774

American (AMR) AF: 0.00 AC: 0 AN: 4128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5768

East Asian (EAS) AF: 0.00 AC: 0 AN: 5542

South Asian (SAS) AF: 0.00 AC: 0 AN: 19502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 775684

Other (OTH) AF: 0.00 AC: 0 AN: 28662

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-1.1
PromoterAI		0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4796715; hg19: chr17-39993771;