rs563320737

Variant names:

• chr22-50548228-C-A
• rs563320737
• NM_138433.5:c.1985C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50548228-C-A
• chr22-50548228-C-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.1985C>A​(p.Ala662Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,550,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: KLHDC7B NM_138433.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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=0.08313149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.1985C>A	p.Ala662Glu	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.1985C>A	p.Ala662Glu	missense_variant	Exon 1 of 1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000395676.4	c.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 1	6		ENSP00000379034.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1398020 Hom.: 0 Cov.: 34 AF XY: 0.00000290 AC XY: 2 AN XY: 689418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000253

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74400

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.5
DANN	Benign	0.94
DEOGEN2	Benign	0.0048	.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.37	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.97	.;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.77	.;N
REVEL	Benign	0.17
Sift	Uncertain	0.0090	.;D
Sift4G	Uncertain	0.019	.;D
Polyphen		0.65	.;P
Vest4		0.18
MutPred		0.14		.;Gain of solvent accessibility (P = 0.005);
MVP		0.71
ClinPred		0.23	T
GERP RS		2.8
Varity_R		0.10
gMVP		0.20

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: rs563320737; hg19: chr22-50986657;