NM_001040192.3:c.1115G>A

Variant names:

• chr21-33488279-C-T
• rs200537192
• NM_001040192.3:c.1115G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040192.3(DNAJC28):​c.1115G>A​(p.Gly372Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,534,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: DNAJC28 NM_001040192.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

DNAJC28 (HGNC:1297): (DnaJ heat shock protein family (Hsp40) member C28) This gene encodes a member of the DnaJ heat shock protein family. The encoded protein, which contains a conserved N-terminal DnaJ domain, is thought to play a role in protein folding or act as a molecular chaperone protein. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10604015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC28	NM_001040192.3	c.1115G>A	p.Gly372Asp	missense_variant	Exon 2 of 2	ENST00000381947.4	NP_001035282.1
DNAJC28	NM_001320746.3	c.1115G>A	p.Gly372Asp	missense_variant	Exon 2 of 2		NP_001307675.1
DNAJC28	NM_017833.5	c.1115G>A	p.Gly372Asp	missense_variant	Exon 2 of 2		NP_060303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC28	ENST00000381947.4	c.1115G>A	p.Gly372Asp	missense_variant	Exon 2 of 2	1	NM_001040192.3	ENSP00000371373.3
DNAJC28	ENST00000314399.3	c.1115G>A	p.Gly372Asp	missense_variant	Exon 2 of 2	1		ENSP00000320303.3
DNAJC28	ENST00000402202.1	c.1115G>A	p.Gly372Asp	missense_variant	Exon 2 of 2	5		ENSP00000385777.1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 151910 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

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: 0.000206

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000118 AC: 22 AN: 186792 AF XY: 0.000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000234

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000156 AC: 216 AN: 1382356 Hom.: 0 Cov.: 30 AF XY: 0.000154 AC XY: 105 AN XY: 682998

African (AFR) AF: 0.0000333 AC: 1 AN: 30056

American (AMR) AF: 0.0000390 AC: 1 AN: 25656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21674

East Asian (EAS) AF: 0.00 AC: 0 AN: 38258

South Asian (SAS) AF: 0.00 AC: 0 AN: 72032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 0.000193 AC: 209 AN: 1081690

Other (OTH) AF: 0.0000882 AC: 5 AN: 56712

GnomAD4 genome AF: 0.000132 AC: 20 AN: 152026 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74330

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.000262 AC: 4 AN: 15258

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.000181

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000148 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 08, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1115G>A (p.G372D) alteration is located in exon 2 (coding exon 1) of the DNAJC28 gene. This alteration results from a G to A substitution at nucleotide position 1115, causing the glycine (G) at amino acid position 372 to be replaced by an aspartic acid (D). 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	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0023	T;T;T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PhyloP100		1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.60	.;N;N;N
REVEL	Benign	0.032
Sift	Benign	0.17	.;T;T;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.78	P;P;P;P
Vest4		0.35
MVP		0.26
MPC		0.059
ClinPred		0.043	T
GERP RS		2.4
Varity_R		0.068
gMVP		0.63
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs200537192; hg19: chr21-34860586;