15-85770563-CT-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022480.4(KLHL25):c.-10-744_-10-743insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL25 NM_022480.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

KLHL25 (HGNC:25732): (kelch like family member 25) Involved in protein ubiquitination; regulation of translational initiation; and ubiquitin-dependent protein catabolic process. Located in cytoplasm. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR1276 (HGNC:35347): (microRNA 1276) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL25	NM_022480.4	c.-10-744_-10-743insA		intron_variant		ENST00000337975.6
MIR1276	NR_031682.1	n.15_16insA		non_coding_transcript_exon_variant	1/1
KLHL25	XM_047432937.1	c.-10-744_-10-743insA		intron_variant
KLHL25	XM_047432938.1	c.-10-744_-10-743insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL25	ENST00000337975.6	c.-10-744_-10-743insA		intron_variant		1	NM_022480.4	P1
MIR1276	ENST00000408707.1	n.15_16insA		mature_miRNA_variant	1/1
KLHL25	ENST00000559131.1	n.154-9553_154-9552insA		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs34381260; hg19: chr15-86313794;