22-50548022-T-C

Variant names:

• chr22-50548022-T-C
• rs1289959855
• NM_138433.5:c.1779T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_138433.5(KLHDC7B):​c.1779T>C​(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P593P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLHDC7B NM_138433.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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>C	p.Pro593Pro	synonymous	Exon 1 of 1	NP_612442.3	A0A3B3ISF6
	KLHDC7B-DT	NR_199716.1		n.52+874A>G		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000272 AC: 2 AN: 73638 Hom.: 0 Cov.: 0 AF XY: 0.0000252 AC XY: 1 AN XY: 39606

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

African (AFR) AF: 0.00 AC: 0 AN: 2730

American (AMR) AF: 0.00 AC: 0 AN: 3270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1546

East Asian (EAS) AF: 0.00 AC: 0 AN: 2744

South Asian (SAS) AF: 0.0000907 AC: 1 AN: 11022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0000218 AC: 1 AN: 45882

Other (OTH) AF: 0.00 AC: 0 AN: 3454

⚠️ 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.

GnomAD4 genome Cov.: 15

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-0.93
PromoterAI		0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1289959855; hg19: chr22-50986451;