10-119838634-T-G

Variant names:

• chr10-119838634-T-G
• rs138353467
• NM_001256378.2:c.1309A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256378.2(MCMBP):​c.1309A>C​(p.Thr437Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T437A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0110

Genes affected

MCMBP (HGNC:25782): (minichromosome maintenance complex binding protein) This gene encodes a protein which is a component of the hexameric minichromosome maintenance (MCM) complex which regulates initiation and elongation of DNA. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

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=0.22891986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCMBP	NM_001256378.2	c.1309A>C	p.Thr437Pro	missense_variant	Exon 12 of 16	ENST00000369077.4	NP_001243307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCMBP	ENST00000369077.4	c.1309A>C	p.Thr437Pro	missense_variant	Exon 12 of 16	1	NM_001256378.2	ENSP00000358073.3
MCMBP	ENST00000360003.7	c.1315A>C	p.Thr439Pro	missense_variant	Exon 12 of 16	2		ENSP00000353098.3
MCMBP	ENST00000466047.5	n.1411A>C		non_coding_transcript_exon_variant	Exon 12 of 16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1315A>C (p.T439P) alteration is located in exon 12 (coding exon 12) of the MCMBP gene. This alteration results from a A to C substitution at nucleotide position 1315, causing the threonine (T) at amino acid position 439 to be replaced by a proline (P). 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	0.25
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.4	N;N
REVEL	Benign	0.18
Sift	Benign	0.042	D;D
Sift4G	Benign	0.080	T;T
Polyphen		0.95	P;.
Vest4		0.39
MutPred		0.53		Loss of phosphorylation at T439 (P = 0.0641);.;
MVP		0.15
MPC		0.83
ClinPred		0.79	D
GERP RS		1.9
Varity_R		0.27
gMVP		0.60

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

Other links and lift over

dbSNP: rs138353467; hg19: chr10-121598146;