1-15536581-A-G

Variant summary

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

The NM_015291.4(DNAJC16):c.341A>G(p.His114Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAJC16 NM_015291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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=0.24533457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC16	NM_015291.4	c.341A>G	p.His114Arg	missense_variant	4/15	ENST00000375847.8
DNAJC16	NM_001287811.2	c.-596A>G		5_prime_UTR_variant	3/14
DNAJC16	NR_109898.2	n.470A>G		non_coding_transcript_exon_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC16	ENST00000375847.8	c.341A>G	p.His114Arg	missense_variant	4/15	1	NM_015291.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Mar 02, 2023

The c.341A>G (p.H114R) alteration is located in exon 4 (coding exon 3) of the DNAJC16 gene. This alteration results from a A to G substitution at nucleotide position 341, causing the histidine (H) at amino acid position 114 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	20
Dann	Benign	0.95
DEOGEN2	Benign	0.026	T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.019
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	0.77	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.38
MutPred		0.35		Gain of MoRF binding (P = 0.052);Gain of MoRF binding (P = 0.052);Gain of MoRF binding (P = 0.052);
MVP		0.74
MPC		0.20
ClinPred		0.50	T
GERP RS		4.8
Varity_R		0.17
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-15863076;