chr13-70107613-G-C

Variant names:

• chr13-70107613-G-C
• rs191673952
• NM_020866.3:c.87C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_020866.3(KLHL1):​c.87C>G​(p.Thr29Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,587,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: KLHL1 NM_020866.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -7.16
• Publications: 0 publications found

Genes affected

KLHL1 (HGNC:6352): (kelch like family member 1) The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

ATXN8OS (HGNC:10561): (ATXN8 opposite strand lncRNA) This gene is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A TAC/TGC trinucleotide repeat expansion that is incorporated into this gene transcript, but not the KLHL1 transcript, causes spinocerebellar ataxia type 8. Presumably the expansion interferes with normal antisense function of this transcript. [provided by RefSeq, Oct 2008]

ATXN8OS Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 8

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 13-70107613-G-C is Benign according to our data. Variant chr13-70107613-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3039726.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-7.16 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020866.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	NM_020866.3	MANE Select	c.87C>G	p.Thr29Thr	synonymous	Exon 1 of 11	NP_065917.1	Q9NR64
	KLHL1	NM_001286725.2		c.87C>G	p.Thr29Thr	synonymous	Exon 1 of 10	NP_001273654.1	F5H1J3
	ATXN8OS	NR_002717.3		n.193G>C		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	ENST00000377844.9	TSL:1 MANE Select	c.87C>G	p.Thr29Thr	synonymous	Exon 1 of 11	ENSP00000367075.4	Q9NR64
	KLHL1	ENST00000545028.2	TSL:2	c.87C>G	p.Thr29Thr	synonymous	Exon 1 of 10	ENSP00000439602.2	F5H1J3
	ATXN8OS	ENST00000414504.6	TSL:5	n.401G>C		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000223 AC: 49 AN: 219882 AF XY: 0.000185

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00277

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000279 AC: 40 AN: 1435140 Hom.: 0 Cov.: 33 AF XY: 0.0000239 AC XY: 17 AN XY: 712078

African (AFR) AF: 0.00 AC: 0 AN: 32650

American (AMR) AF: 0.00 AC: 0 AN: 41206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23544

East Asian (EAS) AF: 0.000934 AC: 37 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 81382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099968

Other (OTH) AF: 0.0000338 AC: 2 AN: 59144

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41598

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KLHL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.011
DANN	Benign	0.57
PhyloP100		-7.2

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: rs191673952; hg19: chr13-70681745;