chr12-55822404-A-T

Variant names:

• chr12-55822404-A-T
• NM_032364.6:c.1867T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032364.6(DNAJC14):​c.1867T>A​(p.Ser623Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC14 NM_032364.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32201487).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032364.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC14	NM_032364.6	MANE Select	c.1867T>A	p.Ser623Thr	missense	Exon 6 of 7	NP_115740.5
	DNAJC14	NM_001394687.1		c.1867T>A	p.Ser623Thr	missense	Exon 6 of 7	NP_001381616.1	Q6Y2X3
	DNAJC14	NM_001394688.1		c.1867T>A	p.Ser623Thr	missense	Exon 6 of 7	NP_001381617.1	Q6Y2X3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC14	ENST00000678005.2	MANE Select	c.1867T>A	p.Ser623Thr	missense	Exon 6 of 7	ENSP00000504134.1	Q6Y2X3
	ENSG00000257390	ENST00000546837.5	TSL:2	c.754T>A	p.Ser252Thr	missense	Exon 5 of 16	ENSP00000447000.1	H0YHG0
	DNAJC14	ENST00000317287.5	TSL:2	c.1867T>A	p.Ser623Thr	missense	Exon 6 of 7	ENSP00000317500.5	Q6Y2X3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
PhyloP100		1.5
Varity_R		0.25
gMVP		0.53
Mutation Taster		=77/23	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-56216188;