Variant 1-15544435-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015291.4(DNAJC16):c.611G>A(p.Arg204Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

DNAJC16
NM_015291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

Variant links:

Genes affected

DNAJC16 (HGNC:29157): (DnaJ heat shock protein family (Hsp40) member C16) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAJC16	NM_015291.4 linkuse as main transcript	c.611G>A	p.Arg204Lys	missense_variant	5/15	ENST00000375847.8	NP_056106.1
DNAJC16	NM_001287811.2 linkuse as main transcript	c.-326G>A		5_prime_UTR_variant	4/14		NP_001274740.1
DNAJC16	NR_109898.2 linkuse as main transcript	n.740G>A		non_coding_transcript_exon_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC16	ENST00000375847.8 linkuse as main transcript	c.611G>A	p.Arg204Lys	missense_variant	5/15	1	NM_015291.4	ENSP00000365007	P1	Q9Y2G8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251246

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Apr 16, 2024

The c.611G>A (p.R204K) alteration is located in exon 5 (coding exon 4) of the DNAJC16 gene. This alteration results from a G to A substitution at nucleotide position 611, causing the arginine (R) at amino acid position 204 to be replaced by a lysine (K). 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

0.15

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0022

T;T;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

.;T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

.;L;.

MutationTaster

Benign

0.83

N;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.32

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.70

MutPred

0.34

Gain of ubiquitination at R204 (P = 0.0192);Gain of ubiquitination at R204 (P = 0.0192);Gain of ubiquitination at R204 (P = 0.0192);

MVP

0.56

MPC

0.68

ClinPred

0.86

GERP RS

6.2

Varity_R

0.18

gMVP

0.76

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