rs370351978

Variant names:

• chr15-78280397-C-A
• rs370351978
• NM_001130182.2:c.1131C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78280397-C-A
• chr15-78280397-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130182.2(DNAJA4):​c.1131C>A​(p.His377Gln) 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: 34)
• Consequence: DNAJA4 NM_001130182.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.599
• Publications: 0 publications found

Genes affected

DNAJA4 (HGNC:14885): (DnaJ heat shock protein family (Hsp40) member A4) Enables chaperone binding activity and unfolded protein binding activity. Involved in several processes, including negative regulation of endothelial cell migration; negative regulation of inclusion body assembly; and protein refolding. Located in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

SKIC8 (HGNC:30300): (SKI8 subunit of superkiller complex) WDR61 is a subunit of the human PAF and SKI complexes, which function in transcriptional regulation and are involved in events downstream of RNA synthesis, such as RNA surveillance (Zhu et al., 2005 [PubMed 16024656]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041030914).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130182.2. 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
	DNAJA4	NM_001130182.2	MANE Select	c.1131C>A	p.His377Gln	missense	Exon 7 of 7	NP_001123654.1	Q8WW22-1
	DNAJA4	NM_018602.4		c.1218C>A	p.His406Gln	missense	Exon 8 of 8	NP_061072.3
	DNAJA4	NM_001387384.1		c.1185C>A	p.His395Gln	missense	Exon 9 of 9	NP_001374313.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJA4	ENST00000394852.8	TSL:1 MANE Select	c.1131C>A	p.His377Gln	missense	Exon 7 of 7	ENSP00000378321.3	Q8WW22-1
	DNAJA4	ENST00000394855.7	TSL:1	c.1218C>A	p.His406Gln	missense	Exon 8 of 8	ENSP00000378324.3	Q8WW22-2
	DNAJA4	ENST00000446172.2	TSL:1	c.1050C>A	p.His350Gln	missense	Exon 7 of 7	ENSP00000413499.2	Q8WW22-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.80
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.60
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.088
Sift	Benign	0.90	T
Sift4G	Benign	0.75	T
Polyphen		0.0010	B
Vest4		0.059
MutPred		0.30		Loss of helix (P = 0.0376)
MVP		0.41
MPC		0.26
ClinPred		0.072	T
GERP RS		2.8
Varity_R		0.058
gMVP		0.28

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: rs370351978; hg19: chr15-78572739;