chr22-50546968-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 6/8 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
• Publications: 0 publications found

Genes affected

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

KLHDC7B-DT (HGNC:53791): (KLHDC7B divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 3770568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	NM_138433.5	MANE Select	c.725C>T	p.Ala242Val	missense	Exon 1 of 1	NP_612442.3	A0A3B3ISF6
	KLHDC7B-DT	NR_199716.1		n.53-500G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	ENST00000648057.3	MANE Select	c.725C>T	p.Ala242Val	missense	Exon 1 of 1	ENSP00000497256.1	A0A3B3ISF6
	KLHDC7B	ENST00000434237.1	TSL:3	n.72+482C>T		intron	N/A
	KLHDC7B-DT	ENST00000796178.1		n.100-500G>A		intron	N/A

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

African (AFR) AF: 0.00142 AC: 59 AN: 41432

American (AMR) AF: 0.00289 AC: 44 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00143 AC: 15 AN: 10460

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00764 AC: 518 AN: 67792

Other (OTH) AF: 0.00238 AC: 5 AN: 2102

Alfa AF: 0.00572 Hom.: 0

Bravo AF: 0.00454

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
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
PhyloP100		-1.5
GERP RS		-8.1
gMVP		0.031

Splicing

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

Other links and lift over

dbSNP: rs556302259; hg19: chr22-50985397;