5-140673319-G-T

Variant names:

• chr5-140673319-G-T
• rs139029027
• NM_194249.3:c.94C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194249.3(DND1):​c.94C>A​(p.Arg32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

DND1 (HGNC:23799): (DND microRNA-mediated repression inhibitor 1) This gene encodes a protein that binds to microRNA-targeting sequences of mRNAs, inhibiting microRNA-mediated repression. Reduced expression of this gene has been implicated in tongue squamous cell carcinoma. Two pseudogenes of this gene are located on the long arm of chromosome 17. [provided by RefSeq, Dec 2010]

HARS1 (HGNC:4816): (histidyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

WDR55 (HGNC:25971): (WD repeat domain 55) Predicted to be involved in rRNA processing. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12004581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DND1	NM_194249.3	c.94C>A	p.Arg32Ser	missense_variant	Exon 2 of 4	ENST00000542735.2	NP_919225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2	c.94C>A	p.Arg32Ser	missense_variant	Exon 2 of 4	1	NM_194249.3	ENSP00000445366.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.062
Sift	Benign	0.25	T
Sift4G	Benign	0.73	T
Polyphen		0.0040	B
Vest4		0.22
MutPred		0.40		Gain of sheet (P = 0.0101);
MVP		0.28
MPC		0.81
ClinPred		0.37	T
GERP RS		4.6
Varity_R		0.17
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs139029027; hg19: chr5-140052904;