NM_138401.4:c.368G>C

Variant names:

• chr19-17422413-G-C
• NM_138401.4:c.368G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138401.4(MVB12A):​c.368G>C​(p.Arg123Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MVB12A NM_138401.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

Genes affected

MVB12A (HGNC:25153): (multivesicular body subunit 12A) Enables lipid binding activity and ubiquitin binding activity. Involved in regulation of epidermal growth factor receptor signaling pathway; viral budding; and virus maturation. Located in several cellular components, including Golgi apparatus; centrosome; and nucleoplasm. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269481 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37724555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12A	NM_138401.4	c.368G>C	p.Arg123Pro	missense_variant	Exon 4 of 9	ENST00000317040.12	NP_612410.1
MVB12A	NM_001304547.2	c.92G>C	p.Arg31Pro	missense_variant	Exon 5 of 10		NP_001291476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVB12A	ENST00000317040.12	c.368G>C	p.Arg123Pro	missense_variant	Exon 4 of 9	1	NM_138401.4	ENSP00000324810.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.089	T;T;T;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.78	.;T;.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;.;L;.;L
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.6	D;.;D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.018	D;.;D;D;D
Sift4G	Benign	0.076	T;T;D;D;D
Polyphen		0.30	.;.;B;.;B
Vest4		0.80, 0.79
MutPred		0.68		.;.;Loss of catalytic residue at R123 (P = 0.0166);Loss of catalytic residue at R123 (P = 0.0166);Loss of catalytic residue at R123 (P = 0.0166);
MVP		0.42
MPC		0.83
ClinPred		0.98	D
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.69
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17533222;