chr5-139426249-T-G

Variant names:

• chr5-139426249-T-G
• NM_152686.4:c.482A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152686.4(DNAJC18):​c.482A>C​(p.Asn161Thr) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC18 NM_152686.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.260
• Publications: 0 publications found

Genes affected

DNAJC18 (HGNC:28429): (DnaJ heat shock protein family (Hsp40) member C18) Predicted to enable Hsp70 protein binding activity. Predicted to be involved in cellular response to misfolded protein; chaperone cofactor-dependent protein refolding; and ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11646366).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152686.4. 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
	DNAJC18	NM_152686.4	MANE Select	c.482A>C	p.Asn161Thr	missense	Exon 4 of 8	NP_689899.1	Q9H819

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC18	ENST00000302060.10	TSL:1 MANE Select	c.482A>C	p.Asn161Thr	missense	Exon 4 of 8	ENSP00000302843.5	Q9H819
	DNAJC18	ENST00000928618.1		c.509A>C	p.Asn170Thr	missense	Exon 5 of 9	ENSP00000598677.1
	DNAJC18	ENST00000886188.1		c.482A>C	p.Asn161Thr	missense	Exon 4 of 8	ENSP00000556247.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.26
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.057
Sift	Benign	0.055	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.29
MutPred		0.30		Gain of phosphorylation at N161 (P = 0.0041)
MVP		0.61
MPC		0.39
ClinPred		0.10	T
GERP RS		-3.1
PromoterAI		0.011	Neutral
Varity_R		0.082
gMVP		0.55
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr5-138761938;