rs762294145

Variant names:

• chr9-34990777-T-G
• rs762294145
• NM_001349723.3:c.147T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001349723.3(DNAJB5):​c.147T>G​(p.Leu49Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,551,500 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: DNAJB5 NM_001349723.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41
• Publications: 0 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-34990777-T-G is Benign according to our data. Variant chr9-34990777-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2659165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BS2: High AC in GnomAd4 at 38 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.147T>G	p.Leu49Leu	synonymous	Exon 2 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135005.3		c.147T>G	p.Leu49Leu	synonymous	Exon 1 of 4	NP_001128477.1	O75953-4
	DNAJB5	NM_001135004.3		c.33T>G	p.Leu11Leu	synonymous	Exon 2 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.147T>G	p.Leu49Leu	synonymous	Exon 2 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000454002.6	TSL:1	c.147T>G	p.Leu49Leu	synonymous	Exon 1 of 4	ENSP00000413684.2	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-35+946T>G		intron	N/A	ENSP00000312517.5	O75953-3

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000237 AC: 36 AN: 151914 AF XY: 0.000248

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.0000810

Gnomad ASJ exome AF: 0.000354

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000521

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000292 AC: 409 AN: 1399378 Hom.: 0 Cov.: 31 AF XY: 0.000298 AC XY: 206 AN XY: 690200

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.000168 AC: 6 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.0000812 AC: 4 AN: 49280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.000348 AC: 375 AN: 1078950

Other (OTH) AF: 0.000259 AC: 15 AN: 58002

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74312

African (AFR) AF: 0.000145 AC: 6 AN: 41416

American (AMR) AF: 0.000458 AC: 7 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000249

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs762294145; hg19: chr9-34990774; COSMIC: COSV56626341; COSMIC: COSV56626341;