chr2-27278189-C-A

Position:

• chr2-27278189-C-A

Variant summary

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

The NM_173650.3(DNAJC5G):​c.377C>A​(p.Thr126Lys) variant causes a missense, splice region 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. 12/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAJC5G NM_173650.3 missense, splice_region
• Scores: Splicing: ADA: 0.05200
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24

Genes affected

DNAJC5G (HGNC:24844): (DnaJ heat shock protein family (Hsp40) member C5 gamma) Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC5G (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=0.22614723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5G	NM_173650.3	c.377C>A	p.Thr126Lys	missense_variant, splice_region_variant	5/7	ENST00000296097.8	NP_775921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5G	ENST00000296097.8	c.377C>A	p.Thr126Lys	missense_variant, splice_region_variant	5/7	2	NM_173650.3	ENSP00000296097.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Apr 25, 2022

The c.377C>A (p.T126K) alteration is located in exon 5 (coding exon 3) of the DNAJC5G gene. This alteration results from a C to A substitution at nucleotide position 377, causing the threonine (T) at amino acid position 126 to be replaced by a lysine (K). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	0.11
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.21	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.80	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.041
Sift	Benign	0.031	D;D
Sift4G	Benign	0.088	T;D
Vest4		0.30
MutPred		0.24		Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.61
ClinPred		0.68	D
GERP RS		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.052
dbscSNV1_RF	Benign	0.36
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: chr2-27501057;