1-6640071-CAAAAAA-CA

Variant names:

• chr1-6640071-CAAAAA-C
• rs56145914
• NM_018198.4:c.1098-19_1098-15delTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018198.4(DNAJC11):​c.1098-19_1098-15delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,136,176 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: DNAJC11 NM_018198.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1098-19_1098-15delTTTTT		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.1098-19_1098-15delTTTTT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1712_1098-1708delTTTTT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5292_741-5288delTTTTT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000255 AC: 29 AN: 1136176 Hom.: 0 AF XY: 0.0000255 AC XY: 14 AN XY: 548326

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

African (AFR) AF: 0.0000414 AC: 1 AN: 24162

American (AMR) AF: 0.000130 AC: 2 AN: 15340

Ashkenazi Jewish (ASJ) AF: 0.0000651 AC: 1 AN: 15358

East Asian (EAS) AF: 0.0000365 AC: 1 AN: 27420

South Asian (SAS) AF: 0.0000200 AC: 1 AN: 50018

European-Finnish (FIN) AF: 0.0000408 AC: 1 AN: 24498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3046

European-Non Finnish (NFE) AF: 0.0000226 AC: 21 AN: 930552

Other (OTH) AF: 0.0000218 AC: 1 AN: 45782

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56145914; hg19: chr1-6700131;