chr10-119842482-T-G

Position:

• chr10-119842482-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001256378.2(MCMBP):​c.1114A>C​(p.Ile372Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38360545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCMBP	NM_001256378.2	c.1114A>C	p.Ile372Leu	missense_variant	10/16	ENST00000369077.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCMBP	ENST00000369077.4	c.1114A>C	p.Ile372Leu	missense_variant	10/16	1	NM_001256378.2	P3
MCMBP	ENST00000360003.7	c.1120A>C	p.Ile374Leu	missense_variant	10/16	2		A1
MCMBP	ENST00000466047.5	n.1216A>C		non_coding_transcript_exon_variant	10/16	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 151958 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000275 AC: 399 AN: 1452150 Hom.: 0 Cov.: 31 AF XY: 0.000235 AC XY: 170 AN XY: 722740

Gnomad4 AFR exome AF: 0.000301

Gnomad4 AMR exome AF: 0.0000673

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.000263

Gnomad4 NFE exome AF: 0.000300

Gnomad4 OTH exome AF: 0.000284

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000263 AC: 4 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.1120A>C (p.I374L) alteration is located in exon 10 (coding exon 10) of the MCMBP gene. This alteration results from a A to C substitution at nucleotide position 1120, causing the isoleucine (I) at amino acid position 374 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.13
Sift	Benign	0.50	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.14	B;.
Vest4		0.46
MutPred		0.72		Gain of catalytic residue at I374 (P = 0.0441);.;
MVP		0.20
MPC		0.31
ClinPred		0.46	T
GERP RS		5.8
Varity_R		0.17
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1852467157; hg19: chr10-121601994;