chr1-6645105-C-T

Position:

• chr1-6645105-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018198.4(DNAJC11):​c.916G>A​(p.Ala306Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAJC11 NM_018198.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15430713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.916G>A	p.Ala306Thr	missense_variant	9/16	ENST00000377577.10
DNAJC11	XM_047424842.1	c.646G>A	p.Ala216Thr	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.916G>A	p.Ala306Thr	missense_variant	9/16	1	NM_018198.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.916G>A (p.A306T) alteration is located in exon 9 (coding exon 9) of the DNAJC11 gene. This alteration results from a G to A substitution at nucleotide position 916, causing the alanine (A) at amino acid position 306 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.60	D;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.029
Sift	Benign	0.13	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.13	B;B
Vest4		0.47
MutPred		0.46		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.14
MPC		0.48
ClinPred		0.35	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-6705165;