2-23562477-C-T

Variant names:

• chr2-23562477-C-T
• rs1667475692
• NM_052920.2:c.281C>T

Variant summary

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

The NM_052920.2(KLHL29):​c.281C>T​(p.Thr94Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000217 in 1,383,436 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T94N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: KLHL29 NM_052920.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• 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=0.27985516).

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.281C>T	p.Thr94Ile	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.281C>T	p.Thr94Ile	missense	Exon 3 of 14	ENSP00000420659.1	Q96CT2-1
	KLHL29	ENST00000489446.1	TSL:1	n.362C>T		non_coding_transcript_exon	Exon 2 of 4
	KLHL29	ENST00000869654.1		c.281C>T	p.Thr94Ile	missense	Exon 2 of 13	ENSP00000539713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1383436 Hom.: 0 Cov.: 32 AF XY: 0.00000293 AC XY: 2 AN XY: 682722

African (AFR) AF: 0.00 AC: 0 AN: 31574

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078704

Other (OTH) AF: 0.00 AC: 0 AN: 57858

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.072	T
Vest4		0.41
MutPred		0.27		Loss of glycosylation at T94 (P = 0.0019)
MVP		0.70
ClinPred		0.82	D
GERP RS		3.8
Varity_R		0.16
gMVP		0.25
Mutation Taster		=76/24	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

dbSNP: rs1667475692; hg19: chr2-23785347;