chr22-50548756-G-A

Position:

• chr22-50548756-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138433.5(KLHDC7B):​c.2513G>A​(p.Gly838Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHDC7B NM_138433.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.933

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.158972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHDC7B	NM_138433.5	c.2513G>A	p.Gly838Glu	missense_variant	1/1	ENST00000648057.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHDC7B	ENST00000648057.3	c.2513G>A	p.Gly838Glu	missense_variant	1/1		NM_138433.5	P3
KLHDC7B	ENST00000395676.4	c.590G>A	p.Gly197Glu	missense_variant	1/1			A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

Jan 24, 2024

The c.590G>A (p.G197E) 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 590, causing the glycine (G) at amino acid position 197 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.94
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.52	T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.48	T
Polyphen		0.84	.;P
Vest4		0.55
MutPred		0.36		.;Loss of MoRF binding (P = 0.0487);
MVP		0.67
ClinPred		0.20	T
GERP RS		1.8
Varity_R		0.14
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-50987185;