Genetic Variant DNAJC16:p.Leu80Phe (chr1-15536478-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_015291.4(DNAJC16):c.238C>T(p.Leu80Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000318 in 1,572,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DNAJC16
NM_015291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC16	NM_015291.4 link	c.238C>T	p.Leu80Phe	missense_variant	Exon 4 of 15	ENST00000375847.8	NP_056106.1	Q9Y2G8-1
DNAJC16	NM_001287811.2 link	c.-699C>T		5_prime_UTR_variant	Exon 3 of 14		NP_001274740.1	Q9Y2G8-2
DNAJC16	NR_109898.2 link	n.367C>T		non_coding_transcript_exon_variant	Exon 4 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC16	ENST00000375847.8 link	c.238C>T	p.Leu80Phe	missense_variant	Exon 4 of 15	1	NM_015291.4	ENSP00000365007.3		Q9Y2G8-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

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

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1420486

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703760

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000365

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238C>T (p.L80F) alteration is located in exon 4 (coding exon 3) of the DNAJC16 gene. This alteration results from a C to T substitution at nucleotide position 238, causing the leucine (L) at amino acid position 80 to be replaced by a phenylalanine (F). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

.;D;D

M_CAP

Uncertain

0.097

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.4

.;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.90

MutPred

0.93

Gain of methylation at K75 (P = 0.0832);Gain of methylation at K75 (P = 0.0832);Gain of methylation at K75 (P = 0.0832);

MVP

0.86

MPC

0.71

ClinPred

0.99

GERP RS

5.8

Varity_R

0.74

gMVP

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