NM_152467.5:c.261C>A

Variant names:

• chr17-41841889-C-A
• NM_152467.5:c.261C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152467.5(KLHL10):​c.261C>A​(p.Pro87Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLHL10 NM_152467.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.261C>A	p.Pro87Pro	synonymous_variant	Exon 2 of 5	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.261C>A	p.Pro87Pro	synonymous_variant	Exon 4 of 7		NP_001316524.1
KLHL10	XM_047435897.1	c.261C>A	p.Pro87Pro	synonymous_variant	Exon 3 of 6		XP_047291853.1
KLHL10	NM_001329596.2	c.-4C>A		5_prime_UTR_variant	Exon 2 of 5		NP_001316525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.261C>A	p.Pro87Pro	synonymous_variant	Exon 2 of 5	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.243C>A	p.Pro81Pro	synonymous_variant	Exon 2 of 2	4		ENSP00000416221.1
KLHL10	ENST00000448203.2	c.261C>A	p.Pro87Pro	synonymous_variant	Exon 4 of 4	4		ENSP00000391983.2
KLHL10	ENST00000485613.1	n.307C>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 58 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39998141;