7-73682663-T-C

Variant names:

• chr7-73682663-T-C
• rs8891
• NM_032317.3:c.*80A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032317.3(DNAJC30):​c.*80A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,495,060 control chromosomes in the GnomAD database, including 134,048 homozygotes. 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: 𝑓 0.36 (10696 hom., cov: 31)
  • Exomes 𝑓: 0.42 (123352 hom.)
• Consequence: DNAJC30 NM_032317.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 19 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]

DNAJC30 Gene-Disease associations (from GenCC):

• Leber hereditary optic neuropathy, autosomal recessive

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC30	NM_032317.3	c.*80A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000395176.3	NP_115693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC30	ENST00000395176.3	c.*80A>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_032317.3	ENSP00000378605.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54651 AN: 151822 Hom.: 10697 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.425 AC: 570502 AN: 1343120 Hom.: 123352 Cov.: 24 AF XY: 0.423 AC XY: 278562 AN XY: 658566

African (AFR) AF: 0.210 AC: 6269 AN: 29854

American (AMR) AF: 0.287 AC: 8377 AN: 29186

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 9028 AN: 20022

East Asian (EAS) AF: 0.309 AC: 11885 AN: 38476

South Asian (SAS) AF: 0.339 AC: 23559 AN: 69552

European-Finnish (FIN) AF: 0.397 AC: 17886 AN: 45086

Middle Eastern (MID) AF: 0.520 AC: 2706 AN: 5200

European-Non Finnish (NFE) AF: 0.446 AC: 467901 AN: 1050258

Other (OTH) AF: 0.413 AC: 22891 AN: 55486

GnomAD4 genome AF: 0.360 AC: 54658 AN: 151940 Hom.: 10696 Cov.: 31 AF XY: 0.356 AC XY: 26462 AN XY: 74252

African (AFR) AF: 0.213 AC: 8837 AN: 41442

American (AMR) AF: 0.321 AC: 4910 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1609 AN: 3466

East Asian (EAS) AF: 0.353 AC: 1814 AN: 5146

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4814

European-Finnish (FIN) AF: 0.389 AC: 4108 AN: 10552

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30438 AN: 67934

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.429 Hom.: 19046

Bravo AF: 0.349

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.28
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs8891; hg19: chr7-73096993; COSMIC: COSV56094456; COSMIC: COSV56094456;