5-140672609-G-C

Position:

• chr5-140672609-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194249.3(DND1):​c.440C>G​(p.Pro147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,610 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: 7.1e-7 (0 hom.)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.119

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052292228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DND1	NM_194249.3	c.440C>G	p.Pro147Arg	missense_variant	3/4	ENST00000542735.2	NP_919225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2	c.440C>G	p.Pro147Arg	missense_variant	3/4	1	NM_194249.3	ENSP00000445366.1
WDR55	ENST00000504897.2	n.*477G>C		non_coding_transcript_exon_variant	8/8	2		ENSP00000439719.1
WDR55	ENST00000504897.2	n.*477G>C		3_prime_UTR_variant	8/8	2		ENSP00000439719.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417610 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 703384

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.440C>G (p.P147R) alteration is located in exon 3 (coding exon 3) of the DND1 gene. This alteration results from a C to G substitution at nucleotide position 440, causing the proline (P) at amino acid position 147 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.021
Sift	Benign	0.43	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.33		Loss of catalytic residue at P146 (P = 0.0131);
MVP		0.38
MPC		0.76
ClinPred		0.056	T
GERP RS		-3.0
Varity_R		0.078
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs527897702; hg19: chr5-140052194;