22-50548660-C-T

Variant names:

• chr22-50548660-C-T
• NM_138433.5:c.2417C>T

Variant summary

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

The NM_138433.5(KLHDC7B):​c.2417C>T​(p.Pro806Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,369,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P806R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: KLHDC7B NM_138433.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=0.15335864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.2417C>T	p.Pro806Leu	missense_variant	Exon 1 of 1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3	c.2417C>T	p.Pro806Leu	missense_variant	Exon 1 of 1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000395676.4	c.494C>T	p.Pro165Leu	missense_variant	Exon 1 of 1	6		ENSP00000379034.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1369204 Hom.: 0 Cov.: 34 AF XY: 0.00000297 AC XY: 2 AN XY: 673770

Gnomad4 AFR exome AF: 0.0000339

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000288

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.37e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.48	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	.;D
Sift4G	Benign	0.088	.;T
Polyphen		0.42	.;B
Vest4		0.13
MutPred		0.30		.;Loss of helix (P = 0.0138);
MVP		0.80
ClinPred		0.40	T
GERP RS		3.1
Varity_R		0.094
gMVP		0.32

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: chr22-50987089;