12-55827601-C-G

Variant names:

• chr12-55827601-C-G
• NM_032364.6:c.1058G>C

Variant summary

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

The NM_032364.6(DNAJC14):​c.1058G>C​(p.Gly353Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. G353V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJC14 NM_032364.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

DNAJC14 (HGNC:24581): (DnaJ heat shock protein family (Hsp40) member C14) Predicted to be involved in protein transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000257390 (HGNC:):

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=0.0904803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC14	NM_032364.6	c.1058G>C	p.Gly353Ala	missense_variant	Exon 2 of 7	ENST00000678005.2	NP_115740.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC14	ENST00000678005.2	c.1058G>C	p.Gly353Ala	missense_variant	Exon 2 of 7		NM_032364.6	ENSP00000504134.1
ENSG00000257390	ENST00000546837.5	c.-56G>C		upstream_gene_variant		2		ENSP00000447000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455658 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723048

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.045	T;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.77	T;.;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.15	N;N;N
REVEL	Benign	0.018
Sift	Benign	0.59	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.15
MutPred		0.33		Gain of catalytic residue at L356 (P = 0);Gain of catalytic residue at L356 (P = 0);Gain of catalytic residue at L356 (P = 0);
MVP		0.29
MPC		0.13
ClinPred		0.097	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.055
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-56221385;