7-73683324-C-T

Variant names:

• chr7-73683324-C-T
• rs1128349
• NM_032317.3:c.100G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BA1

The NM_032317.3(DNAJC30):​c.100G>A​(p.Gly34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,613,630 control chromosomes in the GnomAD database, including 143,552 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10687 hom., cov: 34)
  • Exomes 𝑓: 0.42 (132865 hom.)
• Consequence: DNAJC30 NM_032317.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.486
• Publications: 42 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: Benign. The variant received -19 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, Leber hereditary optic neuropathy, autosomal recessive.
• BP4: Computational evidence support a benign effect (MetaRNN=4.937053E-4).
• BP6: Variant 7-73683324-C-T is Benign according to our data. Variant chr7-73683324-C-T is described in ClinVar as Benign. ClinVar VariationId is 1254123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

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.100G>A	p.Gly34Arg	missense	Exon 1 of 1	NP_115693.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC30	ENST00000395176.3	TSL:6 MANE Select	c.100G>A	p.Gly34Arg	missense	Exon 1 of 1	ENSP00000378605.1
	BUD23	ENST00000855997.1		c.-302C>T		upstream_gene	N/A	ENSP00000526056.1
	BUD23	ENST00000917796.1		c.-302C>T		upstream_gene	N/A	ENSP00000587855.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54664 AN: 152126 Hom.: 10688 Cov.: 34

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.383 AC: 94745 AN: 247294 AF XY: 0.389

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.365

Gnomad FIN exome AF: 0.401

Gnomad NFE exome AF: 0.449

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.422 AC: 616823 AN: 1461386 Hom.: 132865 Cov.: 102 AF XY: 0.421 AC XY: 305935 AN XY: 726980

African (AFR) AF: 0.211 AC: 7061 AN: 33480

American (AMR) AF: 0.279 AC: 12500 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 11305 AN: 26136

East Asian (EAS) AF: 0.309 AC: 12251 AN: 39700

South Asian (SAS) AF: 0.342 AC: 29476 AN: 86258

European-Finnish (FIN) AF: 0.399 AC: 21121 AN: 52926

Middle Eastern (MID) AF: 0.521 AC: 3003 AN: 5766

European-Non Finnish (NFE) AF: 0.445 AC: 495297 AN: 1112000

Other (OTH) AF: 0.411 AC: 24809 AN: 60396

GnomAD4 genome AF: 0.359 AC: 54675 AN: 152244 Hom.: 10687 Cov.: 34 AF XY: 0.356 AC XY: 26505 AN XY: 74420

African (AFR) AF: 0.213 AC: 8865 AN: 41562

American (AMR) AF: 0.321 AC: 4913 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1528 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1823 AN: 5164

South Asian (SAS) AF: 0.332 AC: 1606 AN: 4832

European-Finnish (FIN) AF: 0.390 AC: 4126 AN: 10590

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30469 AN: 68004

Other (OTH) AF: 0.379 AC: 802 AN: 2114

Alfa AF: 0.415 Hom.: 56131

Bravo AF: 0.348

TwinsUK AF: 0.460 AC: 1706

ALSPAC AF: 0.455 AC: 1755

ESP6500AA AF: 0.211 AC: 923

ESP6500EA AF: 0.448 AC: 3837

ExAC AF: 0.383 AC: 46416

Asia WGS AF: 0.298 AC: 1038 AN: 3478

EpiCase AF: 0.452

EpiControl AF: 0.449

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.7
DANN	Benign	0.88
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.00049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.95	L
PhyloP100		-0.49
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.059
Sift	Benign	0.61	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.022
MutPred		0.14		Gain of sheet (P = 0.0507)
MPC		0.47
ClinPred		0.0011	T
GERP RS		-1.8
PromoterAI		-0.038	Neutral
Varity_R		0.044
gMVP		0.20
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1128349; hg19: chr7-73097654; COSMIC: COSV56094402; COSMIC: COSV56094402;