1-6637225-C-T

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.1497G>A(p.Ser499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00881 in 1,614,164 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (90 hom.)
• Consequence: DNAJC11 NM_018198.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.968

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=-0.53).
• BP6: Variant 1-6637225-C-T is Benign according to our data. Variant chr1-6637225-C-T is described in ClinVar as [Benign]. Clinvar id is 774784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.968 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.1497G>A	p.Ser499=	synonymous_variant	14/16	ENST00000377577.10
DNAJC11	XM_047424842.1	c.1227G>A	p.Ser409=	synonymous_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1497G>A	p.Ser499=	synonymous_variant	14/16	1	NM_018198.4	P1

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152166 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00811

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00627 AC: 1576 AN: 251460 Hom.: 12 AF XY: 0.00655 AC XY: 890 AN XY: 135902

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00470

Gnomad FIN exome AF: 0.0157

Gnomad NFE exome AF: 0.00805

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00912 AC: 13330 AN: 1461880 Hom.: 90 Cov.: 31 AF XY: 0.00891 AC XY: 6482 AN XY: 727236

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00286

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00533

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00843

GnomAD4 genome AF: 0.00588 AC: 895 AN: 152284 Hom.: 7 Cov.: 33 AF XY: 0.00647 AC XY: 482 AN XY: 74464

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.0169

Gnomad4 NFE AF: 0.00812

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00733 Hom.: 2

Bravo AF: 0.00486

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00747

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	5.4
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

LitVar

Other links and lift over

dbSNP: rs12134083; hg19: chr1-6697285;