7-73683322-TCC-GCG

Variant names:

• chr7-73683322-TCC-GCG
• NM_032317.3:c.100_102delGGAinsCGC
• DNAJC30 p.Gly34Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_032317.3(DNAJC30):​c.100_102delGGAinsCGC​(p.Gly34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DNAJC30 NM_032317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 0 publications found

Genes affected

DNAJC30 (HGNC:16410): (DnaJ heat shock protein family (Hsp40) member C30) This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. [provided by RefSeq, Jul 2008]

BUD23 (HGNC:16405): (BUD23 rRNA methyltransferase and ribosome maturation factor) This gene encodes a protein containing a nuclear localization signal and an S-adenosyl-L-methionine binding motif typical of methyltransferases, suggesting that the encoded protein may act on DNA methylation. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternatively spliced transcript variants have been found. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: -1.0791 (below the threshold of 3.09). Trascript score misZ: -0.20689 (below the threshold of 3.09). GenCC associations: The gene is linked to Leber hereditary optic neuropathy, autosomal recessive, Leber hereditary optic neuropathy.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032317.3. 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
	DNAJC30	NM_032317.3	MANE Select	c.100_102delGGAinsCGC	p.Gly34Arg	missense	N/A	NP_115693.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC30	ENST00000395176.3	TSL:6 MANE Select	c.100_102delGGAinsCGC	p.Gly34Arg	missense	N/A	ENSP00000378605.1	Q96LL9
	BUD23	ENST00000855997.1		c.-304_-302delTCCinsGCG		upstream_gene	N/A	ENSP00000526056.1
	BUD23	ENST00000917796.1		c.-304_-302delTCCinsGCG		upstream_gene	N/A	ENSP00000587855.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.021

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-73097652;