Genetic Variant NCMAP:p.Pro87Thr (chr1-24605697-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010980.5(NCMAP):c.259C>A(p.Pro87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NCMAP
NM_001010980.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

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]

NCMAP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21202978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCMAP	NM_001010980.5 link	c.259C>A	p.Pro87Thr	missense_variant	Exon 4 of 4	ENST00000374392.3	NP_001010980.1	Q5T1S8
NCMAP	XM_005245872.4 link	c.259C>A	p.Pro87Thr	missense_variant	Exon 4 of 4		XP_005245929.1	Q5T1S8
NCMAP	XM_011541463.3 link	c.259C>A	p.Pro87Thr	missense_variant	Exon 4 of 4		XP_011539765.1	Q5T1S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCMAP	ENST00000374392.3 link	c.259C>A	p.Pro87Thr	missense_variant	Exon 4 of 4	1	NM_001010980.5	ENSP00000363513.2		Q5T1S8
NCMAP	ENST00000486262.1 link	n.432C>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251334

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.259C>A (p.P87T) 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 259, causing the proline (P) at amino acid position 87 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

0.082

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.18

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.72

M_CAP

Benign

0.013

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-6.7

REVEL

Benign

0.19

Sift

Uncertain

0.016

Sift4G

Uncertain

0.036

Polyphen

0.98

Vest4

0.25

MutPred

0.21

Gain of sheet (P = 0.0477);

MVP

0.14

MPC

1.1

ClinPred

0.98

GERP RS

4.8

Varity_R

0.40

gMVP

0.58

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.

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