1-24595462-C-A

Variant summary

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

The NM_001010980.5(NCMAP):​c.32C>A​(p.Thr11Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,050 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: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NCMAP
NM_001010980.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34
Variant links:
Genes affected
NCMAP (HGNC:29332): (non-compact myelin associated protein) Predicted to be a structural constituent of myelin sheath. Predicted to be involved in peripheral nervous system myelin formation and positive regulation of myelination. Predicted to be integral component of plasma membrane. Predicted to be active in Schmidt-Lanterman incisure and paranode region of axon. [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=0.40128827).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCMAPNM_001010980.5 linkc.32C>A p.Thr11Asn missense_variant Exon 2 of 4 ENST00000374392.3 NP_001010980.1 Q5T1S8
NCMAPXM_005245872.4 linkc.32C>A p.Thr11Asn missense_variant Exon 2 of 4 XP_005245929.1 Q5T1S8
NCMAPXM_011541463.3 linkc.32C>A p.Thr11Asn missense_variant Exon 2 of 4 XP_011539765.1 Q5T1S8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCMAPENST00000374392.3 linkc.32C>A p.Thr11Asn missense_variant Exon 2 of 4 1 NM_001010980.5 ENSP00000363513.2 Q5T1S8
NCMAPENST00000486262.1 linkn.200C>A non_coding_transcript_exon_variant Exon 2 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251468
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461718
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
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:
0.0000331
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000170
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.32C>A (p.T11N) alteration is located in exon 1 (coding exon 1) of the NCMAP gene. This alteration results from a C to A substitution at nucleotide position 32, causing the threonine (T) at amino acid position 11 to be replaced by an asparagine (N). 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
0.12
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.15
Sift
Uncertain
0.013
D
Sift4G
Uncertain
0.030
D
Polyphen
0.85
P
Vest4
0.59
MVP
0.12
MPC
0.78
ClinPred
0.96
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.29
gMVP
0.78

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: rs200084084; hg19: chr1-24921953; API