NM_138433.5:c.3390G>C

Variant names:

• chr22-50549633-G-C
• rs140519
• NM_138433.5:c.3390G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138433.5(KLHDC7B):​c.3390G>C​(p.Val1130Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: KLHDC7B NM_138433.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 19 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=2.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.3390G>C	p.Val1130Val	synonymous_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.3390G>C	p.Val1130Val	synonymous_variant	Exon 1 of 1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000395676.4	c.1467G>C	p.Val489Val	synonymous_variant	Exon 1 of 1	6		ENSP00000379034.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.7
DANN	Benign	0.64
PhyloP100		2.7

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

Other links and lift over

dbSNP: rs140519; hg19: chr22-50988062;