1-15546863-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015291.4(DNAJC16):c.856T>A(p.Leu286Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,455,388 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: 0.000012 (0 hom.)
• Consequence: DNAJC16 NM_015291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0100

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14411277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC16	NM_015291.4	c.856T>A	p.Leu286Ile	missense_variant	6/15	ENST00000375847.8
DNAJC16	NM_001287811.2	c.-81T>A		5_prime_UTR_variant	5/14
DNAJC16	NR_109898.2	n.985T>A		non_coding_transcript_exon_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC16	ENST00000375847.8	c.856T>A	p.Leu286Ile	missense_variant	6/15	1	NM_015291.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1455388 Hom.: 0 Cov.: 29 AF XY: 0.00000691 AC XY: 5 AN XY: 724042

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000550

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.856T>A (p.L286I) alteration is located in exon 6 (coding exon 5) of the DNAJC16 gene. This alteration results from a T to A substitution at nucleotide position 856, causing the leucine (L) at amino acid position 286 to be replaced by an isoleucine (I). 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	0.095
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	14
Dann	Benign	0.93
DEOGEN2	Benign	0.023	T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.92	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.028	B;B;.
Vest4		0.28
MutPred		0.36		Gain of methylation at K288 (P = 0.0626);Gain of methylation at K288 (P = 0.0626);Gain of methylation at K288 (P = 0.0626);
MVP		0.53
MPC		0.18
ClinPred		0.26	T
GERP RS		2.0
Varity_R		0.056
gMVP		0.51

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

Other links and lift over

dbSNP: rs1638319425; hg19: chr1-15873358;