Genetic Variant NM_018198.4:c.1599C>T (chr1-6636172-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_018198.4(DNAJC11):c.1599C>T(p.Gly533Gly) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.93

Variant links:

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]

DNAJC11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.93 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC11	NM_018198.4 link	c.1599C>T	p.Gly533Gly	synonymous_variant	Exon 15 of 16	ENST00000377577.10	NP_060668.2	Q9NVH1-1
DNAJC11	XM_047424842.1 link	c.1329C>T	p.Gly443Gly	synonymous_variant	Exon 13 of 14		XP_047280798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC11	ENST00000377577.10 link	c.1599C>T	p.Gly533Gly	synonymous_variant	Exon 15 of 16	1	NM_018198.4	ENSP00000366800.5		Q9NVH1-1

Frequencies

GnomAD3 genomes

AF:

0.00559

AC:

851

AN:

152132

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00529

AC XY:

719

AN XY:

135888

show subpopulations

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.:

Cov.:

AF XY:

0.00857

AC XY:

6231

AN XY:

727242

show subpopulations

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.:

Cov.:

AF XY:

0.00536

AC XY:

399

AN XY:

74444

show subpopulations

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.:

Bravo

AF:

0.00515

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00925

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over