Variant 12-49349383-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304944.2(DNAJC22):c.511G>C(p.Ala171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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

DNAJC22
NM_001304944.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.555

Variant links:

Genes affected

DNAJC22 (HGNC:25802): (DnaJ heat shock protein family (Hsp40) member C22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04364407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC22	NM_001304944.2 linkuse as main transcript	c.511G>C	p.Ala171Pro	missense_variant	3/4	ENST00000549441.7	NP_001291873.1	Q8N4W6A0A024R0Z2
DNAJC22	NM_024902.4 linkuse as main transcript	c.511G>C	p.Ala171Pro	missense_variant	2/3		NP_079178.2	Q8N4W6A0A024R0Z2
DNAJC22	XM_047429555.1 linkuse as main transcript	c.511G>C	p.Ala171Pro	missense_variant	3/6		XP_047285511.1
DNAJC22	XM_047429556.1 linkuse as main transcript	c.511G>C	p.Ala171Pro	missense_variant	3/5		XP_047285512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAJC22	ENST00000549441.7 linkuse as main transcript	c.511G>C	p.Ala171Pro	missense_variant	3/4	2	NM_001304944.2	ENSP00000446830.1	Q8N4W6
DNAJC22	ENST00000395069.3 linkuse as main transcript	c.511G>C	p.Ala171Pro	missense_variant	2/3	1		ENSP00000378508.2	Q8N4W6
DNAJC22	ENST00000647553.1 linkuse as main transcript	n.511G>C		non_coding_transcript_exon_variant	2/4			ENSP00000498036.1	Q8N4W6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244320

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132058

show subpopulations

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 SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453926

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722990

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 31, 2022

The c.511G>C (p.A171P) alteration is located in exon 2 (coding exon 1) of the DNAJC22 gene. This alteration results from a G to C substitution at nucleotide position 511, causing the alanine (A) at amino acid position 171 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.11

DANN

Benign

0.92

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.0055

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.22

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.92

N;N

REVEL

Benign

0.051

Sift

Benign

0.40

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0

B;B

Vest4

0.13

MutPred

0.34

Gain of catalytic residue at E176 (P = 0.0053);Gain of catalytic residue at E176 (P = 0.0053);

MVP

0.15

MPC

0.029

ClinPred

0.047

GERP RS

-2.4

Varity_R

0.052

gMVP

0.58

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