21-33489128-G-A

Variant names:

• chr21-33489128-G-A
• rs767409884
• NM_001040192.3:c.266C>T

Variant summary

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

The NM_001040192.3(DNAJC28):​c.266C>T​(p.Ser89Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S89C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC28 NM_001040192.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC28	NM_001040192.3	c.266C>T	p.Ser89Phe	missense_variant	Exon 2 of 2	ENST00000381947.4	NP_001035282.1
DNAJC28	NM_001320746.3	c.266C>T	p.Ser89Phe	missense_variant	Exon 2 of 2		NP_001307675.1
DNAJC28	NM_017833.5	c.266C>T	p.Ser89Phe	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.266C>T	p.Ser89Phe	missense_variant	Exon 2 of 2	1	NM_001040192.3	ENSP00000371373.3
DNAJC28	ENST00000314399.3	c.266C>T	p.Ser89Phe	missense_variant	Exon 2 of 2	1		ENSP00000320303.3
DNAJC28	ENST00000402202.1	c.266C>T	p.Ser89Phe	missense_variant	Exon 2 of 2	5		ENSP00000385777.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T;T;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	-0.077	T
MutationAssessor	Uncertain	2.1	M;M;M;M
PhyloP100		6.2
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.2	.;D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.016	.;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.97	D;D;D;D
Vest4		0.22
MutPred		0.70		Loss of disorder (P = 0.0311);Loss of disorder (P = 0.0311);Loss of disorder (P = 0.0311);Loss of disorder (P = 0.0311);
MVP		0.80
MPC		0.23
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.32
Mutation Taster		=60/40	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: rs767409884; hg19: chr21-34861435; COSMIC: COSV58721226; COSMIC: COSV58721226;