NM_021800.3:c.*72T>C

Variant names:

• chr10-67797044-A-G
• rs79297589
• NM_021800.3:c.*72T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021800.3(DNAJC12):​c.*72T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,193,816 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (48 hom.)
• Consequence: DNAJC12 NM_021800.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27
• Publications: 2 publications found

Genes affected

DNAJC12 (HGNC:28908): (DnaJ heat shock protein family (Hsp40) member C12) This gene encodes a member of a subclass of the HSP40/DnaJ protein family. Members of this family of proteins are associated with complex assembly, protein folding, and export. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DNAJC12 Gene-Disease associations (from GenCC):

• hyperphenylalaninemia due to DNAJC12 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-67797044-A-G is Benign according to our data. Variant chr10-67797044-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021800.3. 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
	DNAJC12	NM_021800.3	MANE Select	c.*72T>C		3_prime_UTR	Exon 5 of 5	NP_068572.1	Q9UKB3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC12	ENST00000225171.7	TSL:1 MANE Select	c.*72T>C		3_prime_UTR	Exon 5 of 5	ENSP00000225171.2	Q9UKB3-1
	DNAJC12	ENST00000857833.1		c.*72T>C		3_prime_UTR	Exon 3 of 3	ENSP00000527892.1
	DNAJC12	ENST00000857834.1		c.*72T>C		3_prime_UTR	Exon 3 of 3	ENSP00000527893.1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2642 AN: 152180 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00199 AC: 2077 AN: 1041520 Hom.: 48 Cov.: 13 AF XY: 0.00179 AC XY: 938 AN XY: 525078

African (AFR) AF: 0.0607 AC: 1435 AN: 23652

American (AMR) AF: 0.00563 AC: 163 AN: 28958

Ashkenazi Jewish (ASJ) AF: 0.000190 AC: 4 AN: 21012

East Asian (EAS) AF: 0.00 AC: 0 AN: 35436

South Asian (SAS) AF: 0.000108 AC: 7 AN: 64886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50198

Middle Eastern (MID) AF: 0.00374 AC: 18 AN: 4818

European-Non Finnish (NFE) AF: 0.000258 AC: 198 AN: 767302

Other (OTH) AF: 0.00557 AC: 252 AN: 45258

GnomAD4 genome AF: 0.0174 AC: 2647 AN: 152296 Hom.: 67 Cov.: 32 AF XY: 0.0166 AC XY: 1233 AN XY: 74466

African (AFR) AF: 0.0601 AC: 2497 AN: 41562

American (AMR) AF: 0.00648 AC: 99 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68032

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.0103 Hom.: 5

Bravo AF: 0.0211

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.029
DANN	Benign	0.44
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs79297589; hg19: chr10-69556802;