rs778003256

Variant names:

• chr5-140672522-G-A
• NM_194249.3:c.527C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-140672522-G-A
• chr5-140672522-G-C

Variant summary

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

The NM_194249.3(DND1):​c.527C>T​(p.Pro176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,440,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000022 (0 hom.)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09438759).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DND1	NM_194249.3	c.527C>T	p.Pro176Leu	missense_variant	Exon 3 of 4	ENST00000542735.2	NP_919225.1
WDR55	NM_017706.5	c.*2868G>A		downstream_gene_variant		ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.*1290G>A		downstream_gene_variant			XP_005268526.1
WDR55	XM_017009600.3	c.*2868G>A		downstream_gene_variant			XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2	c.527C>T	p.Pro176Leu	missense_variant	Exon 3 of 4	1	NM_194249.3	ENSP00000445366.1
WDR55	ENST00000358337.10	c.*2868G>A		downstream_gene_variant		1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000222 AC: 32 AN: 1440994 Hom.: 0 Cov.: 32 AF XY: 0.0000238 AC XY: 17 AN XY: 715602

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000280

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	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.41	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.050
Sift	Benign	0.24	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.35		Loss of glycosylation at P176 (P = 0.0252);
MVP		0.21
MPC		0.73
ClinPred		0.041	T
GERP RS		0.32
Varity_R		0.13
gMVP		0.39

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: chr5-140052107;