NM_052920.2:c.259A>C

Variant names:

• chr2-23562455-A-C
• NM_052920.2:c.259A>C

Variant summary

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

The NM_052920.2(KLHL29):​c.259A>C​(p.Ser87Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,384,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KLHL29 NM_052920.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

Genes affected

KLHL29 (HGNC:29404): (kelch like family member 29)

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=0.27359152).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052920.2. 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
	KLHL29	NM_052920.2	MANE Select	c.259A>C	p.Ser87Arg	missense	Exon 3 of 14	NP_443152.1	Q96CT2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL29	ENST00000486442.6	TSL:5 MANE Select	c.259A>C	p.Ser87Arg	missense	Exon 3 of 14	ENSP00000420659.1	Q96CT2-1
	KLHL29	ENST00000489446.1	TSL:1	n.340A>C		non_coding_transcript_exon	Exon 2 of 4
	KLHL29	ENST00000869654.1		c.259A>C	p.Ser87Arg	missense	Exon 2 of 13	ENSP00000539713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384170 Hom.: 0 Cov.: 32 AF XY: 0.00000293 AC XY: 2 AN XY: 683164

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35720

South Asian (SAS) AF: 0.00 AC: 0 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078738

Other (OTH) AF: 0.00 AC: 0 AN: 57882

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.063	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.22
Sift	Uncertain	0.020	D
Sift4G	Benign	0.33	T
Vest4		0.29
MutPred		0.30		Loss of glycosylation at S87 (P = 0.0046)
MVP		0.73
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.21
Mutation Taster		=73/27	polymorphism

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

hg19: chr2-23785325;