5-34929813-T-C

Variant names:

• chr5-34929813-T-C
• rs1764517378
• NM_001012339.3:c.-7T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012339.3(DNAJC21):​c.-7T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,186,456 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: DNAJC21 NM_001012339.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 0 publications found

Genes affected

DNAJC21 (HGNC:27030): (DnaJ heat shock protein family (Hsp40) member C21) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the precursor 45S ribosomal RNA and may be involved in early nuclear ribosomal RNA biogenesis and maturation of the 60S ribosomal subunit. Mutations in this gene result in Bone marrow failure syndrome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2017]

DNAJC21 Gene-Disease associations (from GenCC):

• bone marrow failure syndrome 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Shwachman-Diamond syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302970 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC21	NM_001012339.3	c.-7T>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000648817.1	NP_001012339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC21	ENST00000648817.1	c.-7T>C		5_prime_UTR_variant	Exon 1 of 12		NM_001012339.3	ENSP00000497410.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1186456 Hom.: 0 Cov.: 30 AF XY: 0.00000170 AC XY: 1 AN XY: 588832

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23784

American (AMR) AF: 0.00 AC: 0 AN: 27814

Ashkenazi Jewish (ASJ) AF: 0.0000557 AC: 1 AN: 17956

East Asian (EAS) AF: 0.00 AC: 0 AN: 22010

South Asian (SAS) AF: 0.00 AC: 0 AN: 66416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3336

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 944818

Other (OTH) AF: 0.00 AC: 0 AN: 44172

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		-0.83
PromoterAI		0.053	Neutral

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: rs1764517378; hg19: chr5-34929918;