12-55827559-G-T

Position:

• chr12-55827559-G-T

Variant summary

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

The NM_032364.6(DNAJC14):​c.1100C>A​(p.Ser367Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJC14 NM_032364.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC14	NM_032364.6	c.1100C>A	p.Ser367Tyr	missense_variant	2/7	ENST00000678005.2	NP_115740.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC14	ENST00000678005.2	c.1100C>A	p.Ser367Tyr	missense_variant	2/7		NM_032364.6	ENSP00000504134.1
ENSG00000257390	ENST00000546837.5	c.-14C>A		upstream_gene_variant		2		ENSP00000447000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250942 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135632

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454316 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 721656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

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: 0.00

GnomAD4 genome Cov.: 32

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

Mar 31, 2023

The c.1100C>A (p.S367Y) alteration is located in exon 2 (coding exon 1) of the DNAJC14 gene. This alteration results from a C to A substitution at nucleotide position 1100, causing the serine (S) at amino acid position 367 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.77	T;.;.
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.79
MutPred		0.47		Gain of catalytic residue at W368 (P = 0.0031);Gain of catalytic residue at W368 (P = 0.0031);Gain of catalytic residue at W368 (P = 0.0031);
MVP		0.27
MPC		0.62
ClinPred		0.76	D
GERP RS		4.3
Varity_R		0.10
gMVP		0.77

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: rs1249866490; hg19: chr12-56221343;