1-6635271-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018198.4(DNAJC11):c.*404C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 182,400 control chromosomes in the GnomAD database, including 9,950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8398 hom., cov: 33)
  • Exomes 𝑓: 0.32 (1552 hom.)
• Consequence: DNAJC11 NM_018198.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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]

THAP3 (HGNC:20855): (THAP domain containing 3) Predicted to enable DNA binding activity and metal ion binding activity. Involved in positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.*404C>A		3_prime_UTR_variant	16/16	ENST00000377577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.*404C>A		3_prime_UTR_variant	16/16	1	NM_018198.4	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49791 AN: 152056 Hom.: 8389 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.316 AC: 9543 AN: 30226 Hom.: 1552 Cov.: 0 AF XY: 0.327 AC XY: 5147 AN XY: 15734

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.327 AC: 49821 AN: 152174 Hom.: 8398 Cov.: 33 AF XY: 0.327 AC XY: 24353 AN XY: 74380

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.348

Alfa AF: 0.300 Hom.: 2756

Bravo AF: 0.327

Asia WGS AF: 0.399 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.60

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: rs11892; hg19: chr1-6695331; COSMIC: COSV50011287; COSMIC: COSV50011287;