1-15536757-A-G

Variant names:

• chr1-15536757-A-G
• ENST00000616884:c.-420A>G

Variant summary

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

The NM_001287811.2(DNAJC16):​c.-420A>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAJC16 NM_001287811.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC16	NM_015291.4	c.517A>G	p.Ser173Gly	missense_variant	Exon 4 of 15	ENST00000375847.8	NP_056106.1
DNAJC16	NM_001287811.2	c.-420A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 14		NP_001274740.1
DNAJC16	NM_001287811.2	c.-420A>G		5_prime_UTR_variant	Exon 3 of 14		NP_001274740.1
DNAJC16	NR_109898.2	n.646A>G		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	c.517A>G	p.Ser173Gly	missense_variant	Exon 4 of 15	1	NM_015291.4	ENSP00000365007.3

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

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.517A>G (p.S173G) 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 517, causing the serine (S) at amino acid position 173 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	.;L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.032	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.78	P;P;.
Vest4		0.38
MutPred		0.48		Loss of stability (P = 0.1551);Loss of stability (P = 0.1551);Loss of stability (P = 0.1551);
MVP		0.40
MPC		0.16
ClinPred		0.92	D
GERP RS		5.3
Varity_R		0.38
gMVP		0.75

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: chr1-15863252;