rs377035232

Variant names:

• chr5-139420112-G-A
• NM_152686.4:c.893C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-139420112-G-A
• chr5-139420112-G-C

Variant summary

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

The NM_152686.4(DNAJC18):​c.893C>T​(p.Thr298Ile) 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 1,455,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. T298R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJC18 NM_152686.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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

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=0.20127052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC18	NM_152686.4	c.893C>T	p.Thr298Ile	missense_variant	Exon 7 of 8	ENST00000302060.10	NP_689899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC18	ENST00000302060.10	c.893C>T	p.Thr298Ile	missense_variant	Exon 7 of 8	1	NM_152686.4	ENSP00000302843.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455094 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723848

Gnomad4 AFR exome AF: 0.0000304

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.12
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.0	B;.
Vest4		0.17
MutPred		0.47		Loss of disorder (P = 0.057);.;
MVP		0.53
MPC		0.42
ClinPred		0.50	T
GERP RS		3.8
Varity_R		0.13
gMVP		0.61

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: chr5-138755801;