1-24600985-T-C

Variant names:

• chr1-24600985-T-C
• NM_001010980.5:c.128T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010980.5(NCMAP):​c.128T>C​(p.Ile43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCMAP NM_001010980.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010980.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCMAP	NM_001010980.5	MANE Select	c.128T>C	p.Ile43Thr	missense	Exon 3 of 4	NP_001010980.1	Q5T1S8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCMAP	ENST00000374392.3	TSL:1 MANE Select	c.128T>C	p.Ile43Thr	missense	Exon 3 of 4	ENSP00000363513.2	Q5T1S8
	NCMAP	ENST00000870896.1		c.128T>C	p.Ile43Thr	missense	Exon 4 of 5	ENSP00000540955.1
	NCMAP	ENST00000870897.1		c.128T>C	p.Ile43Thr	missense	Exon 4 of 5	ENSP00000540956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0037	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.93	P
Vest4		0.56
MutPred		0.42		Loss of stability (P = 0.0198)
MVP		0.18
MPC		0.43
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.37
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

hg19: chr1-24927476;