rs766511358

Variant names:

• chr2-24963467-C-T
• rs766511358
• NM_016544.3:c.178G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016544.3(DNAJC27):​c.178G>A​(p.Val60Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: DNAJC27 NM_016544.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 2 publications found

Genes affected

DNAJC27 (HGNC:30290): (DnaJ heat shock protein family (Hsp40) member C27) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport and positive regulation of MAPK cascade. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.039137095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016544.3. 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
	DNAJC27	NM_016544.3	MANE Select	c.178G>A	p.Val60Ile	missense	Exon 3 of 7	NP_057628.1	Q9NZQ0-1
	DNAJC27	NM_001198559.1		c.178G>A	p.Val60Ile	missense	Exon 3 of 6	NP_001185488.1	Q9NZQ0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC27	ENST00000264711.7	TSL:1 MANE Select	c.178G>A	p.Val60Ile	missense	Exon 3 of 7	ENSP00000264711.2	Q9NZQ0-1
	DNAJC27	ENST00000534855.5	TSL:1	c.178G>A	p.Val60Ile	missense	Exon 3 of 6	ENSP00000440086.2	Q9NZQ0-3
	DNAJC27	ENST00000380809.7	TSL:2	n.178G>A		non_coding_transcript_exon	Exon 3 of 9	ENSP00000370187.3	Q9NZQ0-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251106 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460732 Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11 AN XY: 726682

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000447 AC: 2 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111188

Other (OTH) AF: 0.0000166 AC: 1 AN: 60348

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.066
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.57	N
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.15
Sift	Benign	0.31	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.49		Gain of ubiquitination at K57 (P = 0.1725)
MVP		0.45
MPC		0.19
ClinPred		0.033	T
GERP RS		2.4
Varity_R		0.030
gMVP		0.26
Mutation Taster		=296/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs766511358; hg19: chr2-25186336; COSMIC: COSV53095763;