1-6640071-CAAAAAA-CAAAA

Variant names:

• chr1-6640071-CAA-C
• rs56145914
• NM_018198.4:c.1098-16_1098-15delTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_018198.4(DNAJC11):​c.1098-16_1098-15delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,188,428 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: 𝑓 0.000049 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: DNAJC11 NM_018198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0127 (14043/1105976) while in subpopulation AMR AF= 0.0313 (462/14756). AF 95% confidence interval is 0.029. There are 0 homozygotes in gnomad4_exome. There are 6972 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC11	NM_018198.4	c.1098-16_1098-15delTT		intron_variant	Intron 10 of 15	ENST00000377577.10	NP_060668.2
DNAJC11	XM_047424842.1	c.828-16_828-15delTT		intron_variant	Intron 8 of 13		XP_047280798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1098-16_1098-15delTT		intron_variant	Intron 10 of 15	1	NM_018198.4	ENSP00000366800.5

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 4 AN: 82480 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000479

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0316 AC: 836 AN: 26422 Hom.: 0 AF XY: 0.0300 AC XY: 398 AN XY: 13270

Gnomad AFR exome AF: 0.0370

Gnomad AMR exome AF: 0.0327

Gnomad ASJ exome AF: 0.0328

Gnomad EAS exome AF: 0.0289

Gnomad SAS exome AF: 0.0245

Gnomad FIN exome AF: 0.0262

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0403

GnomAD4 exome AF: 0.0127 AC: 14043 AN: 1105976 Hom.: 0 AF XY: 0.0131 AC XY: 6972 AN XY: 533668

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.0313

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.0123

Gnomad4 FIN exome AF: 0.0339

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.0000485 AC: 4 AN: 82452 Hom.: 0 Cov.: 0 AF XY: 0.0000782 AC XY: 3 AN XY: 38362

Gnomad4 AFR AF: 0.0000500

Gnomad4 AMR AF: 0.000137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000479

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs56145914; hg19: chr1-6700131;