3-42685640-G-T

Variant names:

• chr3-42685640-G-T
• rs772847156
• NM_152393.4:c.22G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152393.4(KLHL40):​c.22G>T​(p.Ala8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHL40 NM_152393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

Genes affected

KLHL40 (HGNC:30372): (kelch like family member 40) This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061121613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL40	NM_152393.4	c.22G>T	p.Ala8Ser	missense_variant	Exon 1 of 6	ENST00000287777.5	NP_689606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL40	ENST00000287777.5	c.22G>T	p.Ala8Ser	missense_variant	Exon 1 of 6	1	NM_152393.4	ENSP00000287777.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000432 AC: 1 AN: 231492 Hom.: 0 AF XY: 0.00000793 AC XY: 1 AN XY: 126090

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.67	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.038
Sift	Benign	0.13	T
Sift4G	Uncertain	0.040	D
Polyphen		0.0090	B
Vest4		0.13
MutPred		0.29		Gain of phosphorylation at A8 (P = 0.0539);
MVP		0.62
MPC		0.60
ClinPred		0.054	T
GERP RS		2.8
Varity_R		0.092
gMVP		0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs772847156; hg19: chr3-42727132;