rs748488397

Variant names:

• chr1-6644613-C-A
• rs748488397
• NM_018198.4:c.1042G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-6644613-C-A
• chr1-6644613-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.1042G>T​(p.Val348Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. V348I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJC11 NM_018198.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=0.22926086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC11	NM_018198.4	c.1042G>T	p.Val348Phe	missense_variant	Exon 10 of 16	ENST00000377577.10	NP_060668.2
DNAJC11	XM_047424842.1	c.772G>T	p.Val258Phe	missense_variant	Exon 8 of 14		XP_047280798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1042G>T	p.Val348Phe	missense_variant	Exon 10 of 16	1	NM_018198.4	ENSP00000366800.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.13
Sift	Benign	0.066	T;T
Sift4G	Uncertain	0.050	T;T
Polyphen		0.19	B;B
Vest4		0.66
MutPred		0.38		Gain of catalytic residue at V348 (P = 0.1277);Gain of catalytic residue at V348 (P = 0.1277);
MVP		0.63
MPC		0.68
ClinPred		0.70	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.65

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: rs748488397; hg19: chr1-6704673;