chr17-41842082-T-G

Variant names:

• chr17-41842082-T-G
• rs782469970
• NM_152467.5:c.454T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152467.5(KLHL10):​c.454T>G​(p.Tyr152Asp) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y152H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLHL10 NM_152467.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39147916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_152467.5	c.454T>G	p.Tyr152Asp	missense_variant	Exon 2 of 5	ENST00000293303.5	NP_689680.2
KLHL10	NM_001329595.1	c.454T>G	p.Tyr152Asp	missense_variant	Exon 4 of 7		NP_001316524.1
KLHL10	NM_001329596.2	c.190T>G	p.Tyr64Asp	missense_variant	Exon 2 of 5		NP_001316525.1
KLHL10	XM_047435897.1	c.454T>G	p.Tyr152Asp	missense_variant	Exon 3 of 6		XP_047291853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL10	ENST00000293303.5	c.454T>G	p.Tyr152Asp	missense_variant	Exon 2 of 5	1	NM_152467.5	ENSP00000293303.4
KLHL10	ENST00000438813.1	c.436T>G	p.Tyr146Asp	missense_variant	Exon 2 of 2	4		ENSP00000416221.1
KLHL10	ENST00000485613.1	n.500T>G		non_coding_transcript_exon_variant	Exon 2 of 2	4
KLHL10	ENST00000448203.2	c.*88T>G		downstream_gene_variant		4		ENSP00000391983.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;T
Eigen	Benign	-0.081
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	-0.035	N;.
PhyloP100		0.50
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.42
Sift	Benign	0.033	D;T
Sift4G	Benign	0.086	T;T
Polyphen		0.64	P;.
Vest4		0.46
MutPred		0.57		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.83
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs782469970; hg19: chr17-39998334;