1-6637211-G-T

Variant names:

• chr1-6637211-G-T
• rs774995067
• NM_018198.4:c.1511C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018198.4(DNAJC11):​c.1511C>A​(p.Thr504Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T504M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJC11 NM_018198.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC11	NM_018198.4	c.1511C>A	p.Thr504Lys	missense_variant	Exon 14 of 16	ENST00000377577.10	NP_060668.2
DNAJC11	XM_047424842.1	c.1241C>A	p.Thr414Lys	missense_variant	Exon 12 of 14		XP_047280798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1511C>A	p.Thr504Lys	missense_variant	Exon 14 of 16	1	NM_018198.4	ENSP00000366800.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.13
Sift	Benign	0.29	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.68	P;B
Vest4		0.77
MutPred		0.43		Loss of ubiquitination at K500 (P = 0.0402);.;
MVP		0.13
MPC		1.1
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774995067; hg19: chr1-6697271;