Variant 1-53797108-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018087.5(NDC1):c.1259T>C(p.Met420Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

NDC1
NM_018087.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

NDC1 (HGNC:25525): (NDC1 transmembrane nucleoporin) A structural constituent of nuclear pore. Involved in nuclear pore complex assembly and nuclear pore localization. Located in actin cytoskeleton; nuclear membrane; and plasma membrane. Part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

NDC1 links:

NDC1 (HGNC:):

NDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.051596254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDC1	NM_018087.5 linkuse as main transcript	c.1259T>C	p.Met420Thr	missense_variant	12/18	ENST00000371429.4	NP_060557.3	Q9BTX1-1
NDC1	NM_001168551.2 linkuse as main transcript	c.1139T>C	p.Met380Thr	missense_variant	12/18		NP_001162023.1	Q9BTX1-5
NDC1	XM_011541766.3 linkuse as main transcript	c.1256T>C	p.Met419Thr	missense_variant	12/18		XP_011540068.1
NDC1	NR_033142.2 linkuse as main transcript	n.1173T>C		non_coding_transcript_exon_variant	11/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDC1	ENST00000371429.4 linkuse as main transcript	c.1259T>C	p.Met420Thr	missense_variant	12/18	1	NM_018087.5	ENSP00000360483.3		Q9BTX1-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251102

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

106

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000890

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2021

The c.1259T>C (p.M420T) alteration is located in exon 12 (coding exon 12) of the NDC1 gene. This alteration results from a T to C substitution at nucleotide position 1259, causing the methionine (M) at amino acid position 420 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.51

M_CAP

Benign

0.011

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.010

REVEL

Benign

0.039

Sift

Benign

0.75

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.25

MVP

0.10

MPC

0.14

ClinPred

0.020

GERP RS

2.8

Varity_R

0.020

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over