Variant chr2-24967258-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_016544.3(DNAJC27):c.123C>T(p.Phe41Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,611,958 control chromosomes in the GnomAD database, including 6,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 3024 hom., cov: 32)

Exomes 𝑓: 0.047 ( 3816 hom. )

Consequence

DNAJC27
NM_016544.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.557

Variant links:

Genes affected

DNAJC27 (HGNC:30290): (DnaJ heat shock protein family (Hsp40) member C27) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport and positive regulation of MAPK cascade. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC27 links:

DNAJC27 (HGNC:):

DNAJC27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=0.557 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC27	NM_016544.3 linkuse as main transcript	c.123C>T	p.Phe41Phe	synonymous_variant	2/7	ENST00000264711.7	NP_057628.1	Q9NZQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC27	ENST00000264711.7 linkuse as main transcript	c.123C>T	p.Phe41Phe	synonymous_variant	2/7	1	NM_016544.3	ENSP00000264711.2		Q9NZQ0-1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19906

AN:

152046

Hom.:

3018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0640

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0726

Gnomad FIN

AF:

0.0167

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0369

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0592

AC:

14875

AN:

251224

Hom.:

1391

AF XY:

0.0548

AC XY:

7436

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.0340

Gnomad ASJ exome

AF:

0.0465

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0710

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0362

Gnomad OTH exome

AF:

0.0488

GnomAD4 exome

AF:

0.0468

AC:

68320

AN:

1459792

Hom.:

3816

Cov.:

AF XY:

0.0466

AC XY:

33834

AN XY:

726370

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.0443

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0699

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.0374

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

AF:

0.131

AC:

19931

AN:

152166

Hom.:

3024

Cov.:

AF XY:

0.126

AC XY:

9403

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.373

Gnomad4 AMR

AF:

0.0639

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0730

Gnomad4 FIN

AF:

0.0167

Gnomad4 NFE

AF:

0.0369

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0543

Hom.:

839

Bravo

AF:

0.146

Asia WGS

AF:

0.0610

AC:

211

AN:

3478

EpiCase

AF:

0.0388

EpiControl

AF:

0.0382

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.3

DANN

Benign

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over