chr9-34993271-C-T

Variant names:

• chr9-34993271-C-T
• rs202119401
• NM_001349723.3:c.254C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001349723.3(DNAJB5):​c.254C>T​(p.Ser85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,094 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: DNAJB5 NM_001349723.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11
• Publications: 4 publications found

Genes affected

DNAJB5 (HGNC:14887): (DnaJ heat shock protein family (Hsp40) member B5) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins. The encoded protein contains an N-terminal DNAJ domain and a C-terminal substrate binding domain but lacks the cysteine-rich domain found in other DNAJ family members. In mice, a multi-protein complex containing this protein, thioredoxin 1, and histone deacetylase 4, serves as a master negative regulator of cardiac hypertrophy. [provided by RefSeq, Mar 2017]

DNAJB5-DT (HGNC:49846): (DNAJB5 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16638878).
• BS2: High AC in GnomAdExome4 at 53 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349723.3. 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
	DNAJB5	NM_001349723.3	MANE Select	c.254C>T	p.Ser85Leu	missense	Exon 3 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135005.3		c.254C>T	p.Ser85Leu	missense	Exon 2 of 4	NP_001128477.1	O75953-4
	DNAJB5	NM_001135004.3		c.140C>T	p.Ser47Leu	missense	Exon 3 of 5	NP_001128476.3	A0A7I2RN43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB5	ENST00000682809.1	MANE Select	c.254C>T	p.Ser85Leu	missense	Exon 3 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000454002.6	TSL:1	c.254C>T	p.Ser85Leu	missense	Exon 2 of 4	ENSP00000413684.2	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.38C>T	p.Ser13Leu	missense	Exon 2 of 4	ENSP00000312517.5	O75953-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251466 AF XY: 0.0000368

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: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74406

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

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	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		3.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.032	D
Polyphen		0.65	P
Vest4		0.36
MVP		0.64
MPC		1.1
ClinPred		0.25	T
GERP RS		5.3
PromoterAI		-0.0056	Neutral
Varity_R		0.16
gMVP		0.19
Mutation Taster		=74/26	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: rs202119401; hg19: chr9-34993268; COSMIC: COSV56627345; COSMIC: COSV56627345;