22-50546968-C-T

Variant names:

• chr22-50546968-C-T
• rs556302259
• NM_138433.5:c.725C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_138433.5(KLHDC7B):​c.725C>T​(p.Ala242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 151,654 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0043 (3 hom., cov: 33)
• Consequence: KLHDC7B NM_138433.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015220463).
• BP6: Variant 22-50546968-C-T is Benign according to our data. Variant chr22-50546968-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.725C>T	p.Ala242Val	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.725C>T	p.Ala242Val	missense_variant	Exon 1 of 1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000434237.1	n.72+482C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.00435 AC: 659 AN: 151546 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00289

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.00240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00435 AC: 659 AN: 151654 Hom.: 3 Cov.: 33 AF XY: 0.00386 AC XY: 286 AN XY: 74104

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00289

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00143

Gnomad4 NFE AF: 0.00764

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00572 Hom.: 0

Bravo AF: 0.00454

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KLHDC7B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.80
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.015	T
GERP RS		-8.1
gMVP		0.031

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs556302259; hg19: chr22-50985397;