rs994114363

Variant names:

• chr1-15529131-C-T
• rs994114363
• NM_015291.4:c.26C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015291.4(DNAJC16):​c.26C>T​(p.Ser9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,528 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: 0.0000048 (0 hom.)
• Consequence: DNAJC16 NM_015291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC16	NM_015291.4	MANE Select	c.26C>T	p.Ser9Phe	missense	Exon 2 of 15	NP_056106.1	Q9Y2G8-1
	DNAJC16	NM_001287811.2		c.-770+2173C>T		intron	N/A	NP_001274740.1	Q9Y2G8-2
	DNAJC16	NR_109898.2		n.155C>T		non_coding_transcript_exon	Exon 2 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC16	ENST00000375847.8	TSL:1 MANE Select	c.26C>T	p.Ser9Phe	missense	Exon 2 of 15	ENSP00000365007.3	Q9Y2G8-1
	DNAJC16	ENST00000375849.5	TSL:1	c.26C>T	p.Ser9Phe	missense	Exon 2 of 15	ENSP00000365009.1	Q5TDH4
	DNAJC16	ENST00000616884.4	TSL:1	c.-770+2173C>T		intron	N/A	ENSP00000480224.1	Q9Y2G8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461528 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727044

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.35	N
REVEL	Uncertain	0.30
Sift	Benign	0.33	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.93	P
Vest4		0.77
MutPred		0.42		Loss of helix (P = 0.0033)
MVP		0.85
MPC		0.70
ClinPred		0.57	D
GERP RS		5.4
Varity_R		0.084
gMVP		0.43
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs994114363; hg19: chr1-15855626;