7-73683181-G-C

Position:

• chr7-73683181-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_032317.3(DNAJC30):​c.243C>G​(p.Asn81Lys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: DNAJC30 NM_032317.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a domain J (size 65) in uniprot entity DJC30_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_032317.3
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC30	NM_032317.3	c.243C>G	p.Asn81Lys	missense_variant	1/1	ENST00000395176.3	NP_115693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC30	ENST00000395176.3	c.243C>G	p.Asn81Lys	missense_variant	1/1	6	NM_032317.3	ENSP00000378605.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.243C>G (p.N81K) alteration is located in exon 1 (coding exon 1) of the DNAJC30 gene. This alteration results from a C to G substitution at nucleotide position 243, causing the asparagine (N) at amino acid position 81 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.085	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.81		Gain of methylation at N81 (P = 0.0033);
MVP		0.60
MPC		1.3
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.79
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-73097511;