rs1369890534

Variant names:

• chr19-18637113-G-A
• rs1369890534
• NM_018316.3:c.59G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18637113-G-A
• chr19-18637113-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018316.3(KLHL26):​c.59G>A​(p.Gly20Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,364,226 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: KLHL26 NM_018316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.855
• Publications: 0 publications found

Genes affected

KLHL26 (HGNC:25623): (kelch like family member 26)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18731025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL26	NM_018316.3	c.59G>A	p.Gly20Asp	missense_variant	Exon 1 of 3	ENST00000300976.9	NP_060786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL26	ENST00000300976.9	c.59G>A	p.Gly20Asp	missense_variant	Exon 1 of 3	1	NM_018316.3	ENSP00000300976.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 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: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1211998 Hom.: 0 Cov.: 31 AF XY: 0.00000170 AC XY: 1 AN XY: 588552

African (AFR) AF: 0.00 AC: 0 AN: 24016

American (AMR) AF: 0.00 AC: 0 AN: 11536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17804

East Asian (EAS) AF: 0.00 AC: 0 AN: 27216

South Asian (SAS) AF: 0.00 AC: 0 AN: 51088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4376

European-Non Finnish (NFE) AF: 0.00000202 AC: 2 AN: 991332

Other (OTH) AF: 0.00 AC: 0 AN: 49418

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.59G>A (p.G20D) alteration is located in exon 1 (coding exon 1) of the KLHL26 gene. This alteration results from a G to A substitution at nucleotide position 59, causing the glycine (G) at amino acid position 20 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.;.
PhyloP100		0.85
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.040	N;.;.
REVEL	Benign	0.21
Sift	Benign	0.044	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.36	B;.;.
Vest4		0.26
MutPred		0.21		Loss of catalytic residue at A19 (P = 0.1169);Loss of catalytic residue at A19 (P = 0.1169);Loss of catalytic residue at A19 (P = 0.1169);
MVP		0.89
MPC		0.75
ClinPred		0.14	T
GERP RS		1.6
PromoterAI		-0.041	Neutral
Varity_R		0.099
gMVP		0.35
Mutation Taster		=86/14	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: rs1369890534; hg19: chr19-18747923;