1-6635063-C-T

Variant names:

• chr1-6635063-C-T
• rs1043681
• NM_018198.4:c.*612G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018198.4(DNAJC11):​c.*612G>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 0.681 in 231,772 control chromosomes in the GnomAD database, including 54,413 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 0.68 (35796 hom., cov: 32)
  • Exomes 𝑓: 0.68 (18617 hom.)
• Consequence: DNAJC11 NM_018198.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 8 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]

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 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.*612G>A		3_prime_UTR	Exon 16 of 16	NP_060668.2	Q9NVH1-1
	THAP3	NM_138350.4		c.*975C>T		3_prime_UTR	Exon 5 of 5	NP_612359.2
	THAP3	NM_001394497.1		c.*975C>T		3_prime_UTR	Exon 5 of 5	NP_001381426.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC11	ENST00000377577.10	TSL:1 MANE Select	c.*612G>A		3_prime_UTR	Exon 16 of 16	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000451196.5	TSL:1	c.741-279G>A		intron	N/A	ENSP00000415871.1	Q5TH61
	DNAJC11	ENST00000954225.1		c.*612G>A		3_prime_UTR	Exon 16 of 16	ENSP00000624284.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103778 AN: 151964 Hom.: 35759 Cov.: 32

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.677 AC: 53936 AN: 79690 Hom.: 18617 Cov.: 4 AF XY: 0.679 AC XY: 27839 AN XY: 40974

African (AFR) AF: 0.710 AC: 2617 AN: 3688

American (AMR) AF: 0.532 AC: 2587 AN: 4864

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 1135 AN: 1498

East Asian (EAS) AF: 0.601 AC: 2818 AN: 4688

South Asian (SAS) AF: 0.740 AC: 6174 AN: 8342

European-Finnish (FIN) AF: 0.597 AC: 1428 AN: 2392

Middle Eastern (MID) AF: 0.837 AC: 169 AN: 202

European-Non Finnish (NFE) AF: 0.685 AC: 34597 AN: 50510

Other (OTH) AF: 0.688 AC: 2411 AN: 3506

GnomAD4 genome AF: 0.683 AC: 103869 AN: 152082 Hom.: 35796 Cov.: 32 AF XY: 0.680 AC XY: 50583 AN XY: 74338

African (AFR) AF: 0.720 AC: 29887 AN: 41482

American (AMR) AF: 0.600 AC: 9168 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2598 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3042 AN: 5166

South Asian (SAS) AF: 0.766 AC: 3693 AN: 4822

European-Finnish (FIN) AF: 0.597 AC: 6312 AN: 10574

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46887 AN: 67984

Other (OTH) AF: 0.716 AC: 1510 AN: 2110

Alfa AF: 0.693 Hom.: 99522

Bravo AF: 0.680

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		-0.15
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: rs1043681; hg19: chr1-6695123; COSMIC: COSV50010755; COSMIC: COSV50010755;