chr1-65317548-G-T

Position:

• chr1-65317548-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256864.2(DNAJC6):​c.193+7610G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,202 control chromosomes in the GnomAD database, including 1,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1464 hom., cov: 33)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

Genes affected

DNAJC6 (HGNC:15469): (DnaJ heat shock protein family (Hsp40) member C6) DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

DNAJC6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.193+7610G>T		intron_variant		ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.23-47087G>T		intron_variant			NP_055602.1
DNAJC6	NM_001256865.2	c.-130-28063G>T		intron_variant			NP_001243794.1
LOC112268227	XR_002958317.2	n.4906-779G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.193+7610G>T		intron_variant		1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18276 AN: 152084 Hom.: 1453 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18334 AN: 152202 Hom.: 1464 Cov.: 33 AF XY: 0.129 AC XY: 9601 AN XY: 74402

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0687 Hom.: 1092

Bravo AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.45

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: rs10493374; hg19: chr1-65783231; COSMIC: COSV54772161;