dbSNP rs775593045: DNAJC16:p.His176Arg (chr1-15536767-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_015291.4(DNAJC16):c.527A>G(p.His176Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,312 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H176L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAJC16
NM_015291.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.04

Publications

0 publications found

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 was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC16	NM_015291.4	MANE Select	c.527A>G	p.His176Arg	missense	Exon 4 of 15	NP_056106.1	Q9Y2G8-1
DNAJC16	NM_001287811.2		c.-410A>G		5_prime_UTR	Exon 3 of 14	NP_001274740.1	Q9Y2G8-2
DNAJC16	NR_109898.2		n.656A>G		non_coding_transcript_exon	Exon 4 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC16	ENST00000375847.8	TSL:1 MANE Select	c.527A>G	p.His176Arg	missense	Exon 4 of 15	ENSP00000365007.3	Q9Y2G8-1
DNAJC16	ENST00000375849.5	TSL:1	c.527A>G	p.His176Arg	missense	Exon 4 of 15	ENSP00000365009.1	Q5TDH4
DNAJC16	ENST00000616884.4	TSL:1	c.-410A>G		5_prime_UTR	Exon 3 of 14	ENSP00000480224.1	Q9Y2G8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249822

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460312

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111546

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

8.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.4

REVEL

Benign

0.28

Sift

Benign

0.14

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.76

MutPred

0.53

Gain of solvent accessibility (P = 1e-04)

MVP

0.61

MPC

0.75

ClinPred

0.72

GERP RS

5.3

Varity_R

0.33

gMVP

0.86

Mutation Taster

=29/71

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over