1-6636172-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018198.4(DNAJC11):c.1599C>T(p.Gly533=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 1,614,122 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (84 hom.)
• Consequence: DNAJC11 NM_018198.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

Genes affected

DNAJC11 (HGNC:25570): (DnaJ heat shock protein family (Hsp40) member C11) Involved in cristae formation. Located in mitochondrial outer membrane and nuclear speck. Part of MIB complex. Colocalizes with MICOS complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-6636172-G-A is Benign according to our data. Variant chr1-6636172-G-A is described in ClinVar as [Benign]. Clinvar id is 713667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.1599C>T	p.Gly533=	synonymous_variant	15/16	ENST00000377577.10
DNAJC11	XM_047424842.1	c.1329C>T	p.Gly443=	synonymous_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1599C>T	p.Gly533=	synonymous_variant	15/16	1	NM_018198.4	P1

Frequencies

GnomAD3 genomes AF: 0.00559 AC: 851 AN: 152132 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00960

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00507 AC: 1275 AN: 251386 Hom.: 6 AF XY: 0.00529 AC XY: 719 AN XY: 135888

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.00689

Gnomad NFE exome AF: 0.00863

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00872 AC: 12747 AN: 1461872 Hom.: 84 Cov.: 31 AF XY: 0.00857 AC XY: 6231 AN XY: 727242

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00230

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000545

Gnomad4 FIN exome AF: 0.00831

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.00676

GnomAD4 genome AF: 0.00559 AC: 851 AN: 152250 Hom.: 2 Cov.: 32 AF XY: 0.00536 AC XY: 399 AN XY: 74444

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00678

Gnomad4 NFE AF: 0.00960

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00682 Hom.: 0

Bravo AF: 0.00515

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00916

EpiControl AF: 0.00925

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.27
Dann	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs139008319; hg19: chr1-6696232; COSMIC: COSV50011041; COSMIC: COSV50011041;