1-6640071-CAAAAAA-CAAAAAAA

Variant names:

• chr1-6640071-C-CA
• rs56145914
• NM_018198.4:c.1098-15dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018198.4(DNAJC11):​c.1098-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (6434 hom., cov: 0)
  • Exomes 𝑓: 0.20 (300 hom.)
• Consequence: DNAJC11 NM_018198.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-6640071-C-CA is Benign according to our data. Variant chr1-6640071-C-CA is described in ClinVar as Benign. ClinVar VariationId is 402790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018198.4. 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
	DNAJC11	NM_018198.4	MANE Select	c.1098-15dupT		intron	N/A	NP_060668.2	Q9NVH1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC11	ENST00000377577.10	TSL:1 MANE Select	c.1098-15_1098-14insT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1708_1098-1707insT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5288_741-5287insT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.466 AC: 38439 AN: 82518 Hom.: 6442 Cov.: 0

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.475

GnomAD2 exomes AF: 0.173 AC: 4575 AN: 26422 AF XY: 0.176

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.214

Gnomad FIN exome AF: 0.0845

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.204 AC: 225843 AN: 1106338 Hom.: 300 Cov.: 0 AF XY: 0.204 AC XY: 108782 AN XY: 533998

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.177 AC: 4180 AN: 23634

American (AMR) AF: 0.164 AC: 2490 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 3300 AN: 15054

East Asian (EAS) AF: 0.239 AC: 6432 AN: 26920

South Asian (SAS) AF: 0.228 AC: 11216 AN: 49128

European-Finnish (FIN) AF: 0.162 AC: 3920 AN: 24182

Middle Eastern (MID) AF: 0.230 AC: 690 AN: 3002

European-Non Finnish (NFE) AF: 0.204 AC: 184645 AN: 904576

Other (OTH) AF: 0.201 AC: 8970 AN: 44654

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.466 AC: 38409 AN: 82490 Hom.: 6434 Cov.: 0 AF XY: 0.465 AC XY: 17866 AN XY: 38396

African (AFR) AF: 0.427 AC: 8541 AN: 20020

American (AMR) AF: 0.431 AC: 3144 AN: 7288

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1238 AN: 2382

East Asian (EAS) AF: 0.573 AC: 1853 AN: 3232

South Asian (SAS) AF: 0.608 AC: 1775 AN: 2920

European-Finnish (FIN) AF: 0.321 AC: 1008 AN: 3144

Middle Eastern (MID) AF: 0.555 AC: 91 AN: 164

European-Non Finnish (NFE) AF: 0.481 AC: 20112 AN: 41794

Other (OTH) AF: 0.473 AC: 536 AN: 1132

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
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: rs56145914; hg19: chr1-6700131;