chr1-15544435-G-C

Variant names:

• chr1-15544435-G-C
• rs767948810
• NM_015291.4:c.611G>C

Variant summary

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

The NM_015291.4(DNAJC16):​c.611G>C​(p.Arg204Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R204K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC16 NM_015291.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• 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.611G>C	p.Arg204Thr	missense	Exon 5 of 15	NP_056106.1	Q9Y2G8-1
	DNAJC16	NM_001287811.2		c.-326G>C		5_prime_UTR	Exon 4 of 14	NP_001274740.1	Q9Y2G8-2
	DNAJC16	NR_109898.2		n.740G>C		non_coding_transcript_exon	Exon 5 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC16	ENST00000375847.8	TSL:1 MANE Select	c.611G>C	p.Arg204Thr	missense	Exon 5 of 15	ENSP00000365007.3	Q9Y2G8-1
	DNAJC16	ENST00000375849.5	TSL:1	c.611G>C	p.Arg204Thr	missense	Exon 5 of 15	ENSP00000365009.1	Q5TDH4
	DNAJC16	ENST00000616884.4	TSL:1	c.-326G>C		5_prime_UTR	Exon 4 of 14	ENSP00000480224.1	Q9Y2G8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0062	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.32
Sift	Benign	0.25	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.83
MutPred		0.36		Gain of helix (P = 0.132)
MVP		0.64
MPC		0.83
ClinPred		0.89	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.82
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767948810; hg19: chr1-15870930;