chr4-99930457-C-T

Variant names:

• chr4-99930457-C-T
• rs1373243869
• NM_001031723.4:c.298G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031723.4(DNAJB14):​c.298G>A​(p.Val100Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,439,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJB14 NM_001031723.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82
• Publications: 0 publications found

Genes affected

DNAJB14 (HGNC:25881): (DnaJ heat shock protein family (Hsp40) member B14) Enables Hsp70 protein binding activity. Involved in cellular protein-containing complex assembly and chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3668635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031723.4. 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
	DNAJB14	NM_001031723.4	MANE Select	c.298G>A	p.Val100Ile	missense	Exon 2 of 8	NP_001026893.1	Q8TBM8-1
	DNAJB14	NM_001278311.2		c.298G>A	p.Val100Ile	missense	Exon 2 of 4	NP_001265240.1	A0A087WWX2
	DNAJB14	NM_001278310.2		c.105-7272G>A		intron	N/A	NP_001265239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB14	ENST00000442697.7	TSL:1 MANE Select	c.298G>A	p.Val100Ile	missense	Exon 2 of 8	ENSP00000404381.2	Q8TBM8-1
	DNAJB14	ENST00000420137.5	TSL:1	n.76G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000416179.1	H7C494
	DNAJB14	ENST00000334223.6	TSL:1	n.134-7272G>A		intron	N/A	ENSP00000335249.2	F2Z2L8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000426 AC: 1 AN: 234722 AF XY: 0.00000786

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: 0.00000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439516 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715482

African (AFR) AF: 0.00 AC: 0 AN: 32598

American (AMR) AF: 0.00 AC: 0 AN: 40940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25388

East Asian (EAS) AF: 0.00 AC: 0 AN: 38942

South Asian (SAS) AF: 0.00 AC: 0 AN: 81546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101854

Other (OTH) AF: 0.00 AC: 0 AN: 59444

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000565 Hom.: 0

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	Uncertain	0.35
BayesDel_addAF	Benign	0.0065	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.34	N
PhyloP100		6.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.19
Sift	Benign	0.059	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.34	B
Vest4		0.56
MutPred		0.30		Loss of helix (P = 0.0626)
MVP		0.52
MPC		1.4
ClinPred		0.61	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.41
Mutation Taster		=53/47	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: rs1373243869; hg19: chr4-100851614;