22-50548279-G-A

Position:

• chr22-50548279-G-A

Variant summary

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

The NM_138433.5(KLHDC7B):​c.2036G>A​(p.Arg679Lys) 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. 16/20 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: 31)
• Consequence: KLHDC7B NM_138433.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.346

Genes affected

KLHDC7B (HGNC:25145): (kelch domain containing 7B)

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=0.043659657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.2036G>A	p.Arg679Lys	missense_variant	1/1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3	c.2036G>A	p.Arg679Lys	missense_variant	1/1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000395676.4	c.113G>A	p.Arg38Lys	missense_variant	1/1	6		ENSP00000379034.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.113G>A (p.R38K) alteration is located in exon 1 (coding exon 1) of the KLHDC7B gene. This alteration results from a G to A substitution at nucleotide position 113, causing the arginine (R) at amino acid position 38 to be replaced by a lysine (K). 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	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.0
DANN	Benign	0.65
DEOGEN2	Benign	0.0038	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.42	.;N
REVEL	Benign	0.15
Sift	Benign	0.73	.;T
Sift4G	Benign	0.99	.;T
Polyphen		0.0	.;B
Vest4		0.062
MutPred		0.15		.;Gain of methylation at R38 (P = 0.0053);
MVP		0.58
ClinPred		0.022	T
GERP RS		-0.10
Varity_R		0.047
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50986708; COSMIC: COSV67464919; COSMIC: COSV67464919;