5-140672667-G-A

Position:

• chr5-140672667-G-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.382C>T​(p.Pro128Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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=0.1222941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DND1	NM_194249.3	c.382C>T	p.Pro128Ser	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.382C>T	p.Pro128Ser	missense_variant	3/4	1	NM_194249.3	ENSP00000445366.1
WDR55	ENST00000504897.2	n.*535G>A		non_coding_transcript_exon_variant	8/8	2		ENSP00000439719.1
WDR55	ENST00000504897.2	n.*535G>A		3_prime_UTR_variant	8/8	2		ENSP00000439719.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 05, 2023

The c.382C>T (p.P128S) alteration is located in exon 3 (coding exon 3) of the DND1 gene. This alteration results from a C to T substitution at nucleotide position 382, causing the proline (P) at amino acid position 128 to be replaced by a serine (S). 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	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.47	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.057
Sift	Benign	0.51	T
Sift4G	Benign	0.43	T
Polyphen		0.049	B
Vest4		0.16
MutPred		0.26		Loss of sheet (P = 0.0181);
MVP		0.31
MPC		0.79
ClinPred		0.21	T
GERP RS		4.8
Varity_R		0.062
gMVP		0.66

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: chr5-140052252;