NM_138433.5:c.725C>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138433.5(KLHDC7B):​c.725C>A​(p.Ala242Asp) variant causes a missense 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. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A242V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHDC7B NM_138433.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08369869).

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>A	p.Ala242Asp	missense	Exon 1 of 1	NP_612442.3	A0A3B3ISF6
	KLHDC7B-DT	NR_199716.1		n.53-500G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	ENST00000648057.3	MANE Select	c.725C>A	p.Ala242Asp	missense	Exon 1 of 1	ENSP00000497256.1	A0A3B3ISF6
	KLHDC7B	ENST00000434237.1	TSL:3	n.72+482C>A		intron	N/A
	KLHDC7B-DT	ENST00000796178.1		n.100-500G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.62
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.084	T
PhyloP100		-1.5
GERP RS		-8.1
gMVP		0.049
Mutation Taster		=100/0	polymorphism

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;