19-18637113-G-T

Variant names:

• chr19-18637113-G-T
• rs1369890534
• NM_018316.3:c.59G>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>T​(p.Gly20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000825 in 1,212,000 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. G20D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: KLHL26 NM_018316.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.1706022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL26	NM_018316.3	c.59G>T	p.Gly20Val	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>T	p.Gly20Val	missense_variant	Exon 1 of 3	1	NM_018316.3	ENSP00000300976.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.25e-7 AC: 1 AN: 1212000 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00000101 AC: 1 AN: 991334

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;.;.
PhyloP100		0.85
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.37	N;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.027	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0060	B;.;.
Vest4		0.15
MutPred		0.26		Loss of glycosylation at P21 (P = 0.1109);Loss of glycosylation at P21 (P = 0.1109);Loss of glycosylation at P21 (P = 0.1109);
MVP		0.81
MPC		0.72
ClinPred		0.14	T
GERP RS		1.6
PromoterAI		-0.086	Neutral
Varity_R		0.091
gMVP		0.29
Mutation Taster		=82/18	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;