chr5-140672589-G-C

Variant names:

• chr5-140672589-G-C
• NM_194249.3:c.460C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194249.3(DND1):​c.460C>G​(p.Leu154Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,423,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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]

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3980264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DND1	NM_194249.3	c.460C>G	p.Leu154Val	missense_variant	Exon 3 of 4	ENST00000542735.2	NP_919225.1
WDR55	NM_017706.5	c.*2935G>C		downstream_gene_variant		ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.*1357G>C		downstream_gene_variant			XP_005268526.1
WDR55	XM_017009600.3	c.*2935G>C		downstream_gene_variant			XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2	c.460C>G	p.Leu154Val	missense_variant	Exon 3 of 4	1	NM_194249.3	ENSP00000445366.1
WDR55	ENST00000358337.10	c.*2935G>C		downstream_gene_variant		1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1423994 Hom.: 0 Cov.: 32 AF XY: 0.00000283 AC XY: 2 AN XY: 706952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.17
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.43		Loss of stability (P = 0.072);
MVP		0.45
MPC		1.3
ClinPred		0.73	D
GERP RS		2.9
Varity_R		0.47
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-140052174;