17-41837519-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001329595.1(KLHL10):​c.-76G>T variant causes a 5 prime UTR premature start codon gain 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)
• Consequence: KLHL10 NM_001329595.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL10	NM_001329595.1	c.-76G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 7		NP_001316524.1
KLHL10	XM_047435897.1	c.-76G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		XP_047291853.1
KLHL10	NM_001329595.1	c.-76G>T		5_prime_UTR_variant	Exon 2 of 7		NP_001316524.1
KLHL10	XM_047435897.1	c.-76G>T		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	c.-76G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	4		ENSP00000391983.2
KLHL10	ENST00000448203	c.-76G>T		5_prime_UTR_variant	Exon 2 of 4	4		ENSP00000391983.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.70

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;