1-53772486-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018087.5(NDC1):​c.1804G>A​(p.Val602Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NDC1
NM_018087.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27306557).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDC1NM_018087.5 linkc.1804G>A p.Val602Ile missense_variant Exon 17 of 18 ENST00000371429.4 NP_060557.3 Q9BTX1-1
NDC1NM_001168551.2 linkc.1684G>A p.Val562Ile missense_variant Exon 17 of 18 NP_001162023.1 Q9BTX1-5
NDC1XM_011541766.3 linkc.1801G>A p.Val601Ile missense_variant Exon 17 of 18 XP_011540068.1
NDC1NR_033142.2 linkn.1718G>A non_coding_transcript_exon_variant Exon 16 of 17

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDC1ENST00000371429.4 linkc.1804G>A p.Val602Ile missense_variant Exon 17 of 18 1 NM_018087.5 ENSP00000360483.3 Q9BTX1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250894
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135606
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000353
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460236
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
726480
show subpopulations
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1804G>A (p.V602I) alteration is located in exon 17 (coding exon 17) of the NDC1 gene. This alteration results from a G to A substitution at nucleotide position 1804, causing the valine (V) at amino acid position 602 to be replaced by an isoleucine (I). 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
0.11
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.030
N
REVEL
Benign
0.15
Sift
Benign
0.084
T
Sift4G
Benign
0.064
T
Polyphen
0.062
B
Vest4
0.42
MutPred
0.50
Gain of methylation at K604 (P = 0.118);
MVP
0.34
MPC
0.27
ClinPred
0.70
D
GERP RS
5.3
Varity_R
0.075
gMVP
0.28

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

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

Other links and lift over

dbSNP: rs770330848; hg19: chr1-54238159; API