15-40767943-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_018163.3(DNAJC17):c.912G>A(p.Thr304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,460,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: DNAJC17 NM_018163.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.799

Genes affected

DNAJC17 (HGNC:25556): (DnaJ heat shock protein family (Hsp40) member C17) Predicted to enable RNA binding activity. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II and toxin transport. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 15-40767943-C-T is Benign according to our data. Variant chr15-40767943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1949982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.799 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC17	NM_018163.3	c.912G>A	p.Thr304=	synonymous_variant	11/11	ENST00000220496.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC17	ENST00000220496.9	c.912G>A	p.Thr304=	synonymous_variant	11/11	1	NM_018163.3	P1
DNAJC17	ENST00000558727.1	n.477G>A		non_coding_transcript_exon_variant	2/2	3
DNAJC17	ENST00000561110.5	n.459G>A		non_coding_transcript_exon_variant	5/5	3
DNAJC17	ENST00000559238.5	c.*940G>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000802 AC: 2 AN: 249500 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134984

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460452 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 726582

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 03, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	4.2
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs760787274; hg19: chr15-41060141; COSMIC: COSV53067321; COSMIC: COSV53067321;