ENST00000396355.5:c.-512T>C

Variant names:

• chr16-15643581-T-C
• rs886051714
• ENST00000396355.5:c.-512T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The ENST00000396355.5(NDE1):​c.-512T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000058 in 310,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: NDE1 ENST00000396355.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 0 publications found

Genes affected

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

MIR484 (HGNC:32341): (microRNA 484) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000885 (14/158142) while in subpopulation SAS AF = 0.000399 (14/35074). AF 95% confidence interval is 0.00024. There are 0 homozygotes in GnomAdExome4. There are 12 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_001143979.2	c.-512T>C		5_prime_UTR_variant	Exon 1 of 10		NP_001137451.1
NDE1	XM_006720897.5	c.-294T>C		5_prime_UTR_variant	Exon 1 of 8		XP_006720960.1
NDE1	XM_047434258.1	c.-294T>C		5_prime_UTR_variant	Exon 1 of 8		XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396355.5	c.-512T>C		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000379643.1
NDE1	ENST00000674888.1	n.-390T>C		upstream_gene_variant				ENSP00000501936.1
MIR484	ENST00000606601.3	n.*209T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000885 AC: 14 AN: 158142 Hom.: 0 Cov.: 0 AF XY: 0.000132 AC XY: 12 AN XY: 90818

African (AFR) AF: 0.00 AC: 0 AN: 1028

American (AMR) AF: 0.00 AC: 0 AN: 2050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4222

East Asian (EAS) AF: 0.00 AC: 0 AN: 1170

South Asian (SAS) AF: 0.000399 AC: 14 AN: 35074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 95682

Other (OTH) AF: 0.00 AC: 0 AN: 7616

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151948 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74226

African (AFR) AF: 0.0000484 AC: 2 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67954

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.69
DANN	Benign	0.41
PhyloP100		-1.4
PromoterAI		0.0024	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs886051714; hg19: chr16-15737438;