Genetic Variant NM_138433.5:c.1779T>A (chr22-50548022-T-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_138433.5(KLHDC7B):c.1779T>A(p.Pro593Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 15)

Exomes 𝑓: 0.0048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLHDC7B
NM_138433.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.933

Publications

0 publications found

Variant links:

Genes affected

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

KLHDC7B links:

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

KLHDC7B-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 22-50548022-T-A is Benign according to our data. Variant chr22-50548022-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2653403.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.933 with no splicing effect.

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.1779T>A	p.Pro593Pro	synonymous	Exon 1 of 1	NP_612442.3	A0A3B3ISF6
	KLHDC7B-DT	NR_199716.1		n.52+874A>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLHDC7B	ENST00000648057.3	MANE Select	c.1779T>A	p.Pro593Pro	synonymous	Exon 1 of 1	ENSP00000497256.1	A0A3B3ISF6
KLHDC7B-DT	ENST00000796178.1		n.99+874A>T		intron	N/A
KLHDC7B-DT	ENST00000796179.1		n.30+802A>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

70558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000428

Gnomad ASJ

AF:

0.000590

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000238

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00478

AC:

351

AN:

73422

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

182

AN XY:

39486

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00331

AC:

AN:

2722

American (AMR)

AF:

0.00306

AC:

AN:

3264

Ashkenazi Jewish (ASJ)

AF:

0.00915

AC:

AN:

1530

East Asian (EAS)

AF:

0.00329

AC:

AN:

2734

South Asian (SAS)

AF:

0.000272

AC:

AN:

11018

European-Finnish (FIN)

AF:

0.00182

AC:

AN:

2744

Middle Eastern (MID)

AF:

0.0174

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00614

AC:

281

AN:

45742

Other (OTH)

AF:

0.00465

AC:

AN:

3438

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.314

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000170

AC:

AN:

70618

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

AN XY:

33882

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

18316

American (AMR)

AF:

0.000427

AC:

AN:

7026

Ashkenazi Jewish (ASJ)

AF:

0.000590

AC:

AN:

1694

East Asian (EAS)

AF:

0.00

AC:

AN:

2666

South Asian (SAS)

AF:

0.00

AC:

AN:

1842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.000238

AC:

AN:

33610

Other (OTH)

AF:

0.00

AC:

AN:

940

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.263

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.51

PhyloP100

-0.93

PromoterAI

0.0018

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over