19-18637083-G-T

Variant names:

• chr19-18637083-G-T
• rs368090804
• NM_018316.3:c.29G>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.29G>T​(p.Gly10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000808 in 1,237,086 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. G10D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: KLHL26 NM_018316.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• 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=0.22037661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL26	NM_018316.3	c.29G>T	p.Gly10Val	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.29G>T	p.Gly10Val	missense_variant	Exon 1 of 3	1	NM_018316.3	ENSP00000300976.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.08e-7 AC: 1 AN: 1237086 Hom.: 0 Cov.: 31 AF XY: 0.00000166 AC XY: 1 AN XY: 603598

African (AFR) AF: 0.0000406 AC: 1 AN: 24610

American (AMR) AF: 0.00 AC: 0 AN: 14642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19310

East Asian (EAS) AF: 0.00 AC: 0 AN: 27368

South Asian (SAS) AF: 0.00 AC: 0 AN: 56724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4200

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1002344

Other (OTH) AF: 0.00 AC: 0 AN: 50462

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.0	N;.;.
PhyloP100		-0.74
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.13	N;.;.
REVEL	Benign	0.23
Sift	Benign	0.055	T;.;.
Sift4G	Benign	0.19	T;D;D
Polyphen		1.0	D;.;.
Vest4		0.13
MutPred		0.35		Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);
MVP		0.87
MPC		0.72
ClinPred		0.28	T
GERP RS		0.52
PromoterAI		0.073	Neutral
Varity_R		0.068
gMVP		0.30
Mutation Taster		=89/11	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: rs368090804; hg19: chr19-18747893;