NM_001010980.5:c.11C>T

Variant summary

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

The NM_001010980.5(NCMAP):​c.11C>T​(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NCMAP
NM_001010980.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.925
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 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=0.049951613).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCMAPNM_001010980.5 linkc.11C>T p.Ala4Val missense_variant Exon 2 of 4 ENST00000374392.3 NP_001010980.1 Q5T1S8
NCMAPXM_005245872.4 linkc.11C>T p.Ala4Val missense_variant Exon 2 of 4 XP_005245929.1 Q5T1S8
NCMAPXM_011541463.3 linkc.11C>T p.Ala4Val 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.11C>T p.Ala4Val missense_variant Exon 2 of 4 1 NM_001010980.5 ENSP00000363513.2 Q5T1S8
NCMAPENST00000486262.1 linkn.179C>T non_coding_transcript_exon_variant Exon 2 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251350
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135846
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1460926
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
726856
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:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
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
Mar 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the NCMAP gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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
0.13
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.50
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.050
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.85
N
REVEL
Benign
0.016
Sift
Benign
0.30
T
Sift4G
Benign
0.80
T
Polyphen
0.0010
B
Vest4
0.21
MutPred
0.23
Gain of sheet (P = 0.039);
MVP
0.067
MPC
0.34
ClinPred
0.13
T
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.073
gMVP
0.59

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: rs763387308; hg19: chr1-24921932; API