5-137618759-CAAAA-CAAAAAAAAAAAAAAAAAA

Variant names:

• chr5-137618759-C-CAAAAAAAAAAAAAA
• rs58917494
• NM_017415.3:c.*3325_*3338dupTTTTTTTTTTTTTT

Variant summary

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

The NM_017415.3(KLHL3):​c.*3325_*3338dupTTTTTTTTTTTTTT variant causes a 3 prime UTR 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: 22)
• Consequence: KLHL3 NM_017415.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

Genes affected

KLHL3 (HGNC:6354): (kelch like family member 3) This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

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 rank	MANE	Protein	UniProt
KLHL3	NM_017415.3	c.*3325_*3338dupTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 15 of 15	ENST00000309755.9	NP_059111.2
KLHL3	NM_001257194.1	c.*3325_*3338dupTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 15 of 15		NP_001244123.1
KLHL3	NM_001257195.2	c.*3325_*3338dupTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 13 of 13		NP_001244124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL3	ENST00000309755	c.*3325_*3338dupTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 15 of 15	1	NM_017415.3	ENSP00000312397.4
KLHL3	ENST00000508657	c.*3325_*3338dupTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000422099.1
KLHL3	ENST00000506491	c.*3325_*3338dupTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000424828.1
KLHL3	ENST00000509694.1	n.623-909_623-896dupTTTTTTTTTTTTTT		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58917494; hg19: chr5-136954448;