22-50548750-T-G

Position:

• chr22-50548750-T-G

Variant summary

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

The NM_138433.5(KLHDC7B):​c.2507T>G​(p.Val836Gly) 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: -0.977

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=0.22956756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.2507T>G	p.Val836Gly	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.2507T>G	p.Val836Gly	missense_variant	1/1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000395676.4	c.584T>G	p.Val195Gly	missense_variant	1/1	6		ENSP00000379034.2

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 27, 2022

The c.584T>G (p.V195G) alteration is located in exon 1 (coding exon 1) of the KLHDC7B gene. This alteration results from a T to G substitution at nucleotide position 584, causing the valine (V) at amino acid position 195 to be replaced by a glycine (G). 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	0.074
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.063	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.25	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	.;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0060	.;D
Sift4G	Uncertain	0.0050	.;D
Polyphen		0.93	.;P
Vest4		0.20
MutPred		0.42		.;Loss of sheet (P = 0.0126);
MVP		0.54
ClinPred		0.40	T
GERP RS		-4.6
Varity_R		0.20
gMVP		0.57

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: chr22-50987179;