chr19-17420319-T-G

Position:

• chr19-17420319-T-G

Variant summary

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

The NM_138401.4(MVB12A):​c.97T>G​(p.Cys33Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MVB12A NM_138401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.252

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]

MVB12A (HGNC:):

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=0.21706077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVB12A	NM_138401.4	c.97T>G	p.Cys33Gly	missense_variant	2/9	ENST00000317040.12	NP_612410.1
MVB12A	NM_001304547.2	c.-180T>G		5_prime_UTR_variant	3/10		NP_001291476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVB12A	ENST00000317040.12	c.97T>G	p.Cys33Gly	missense_variant	2/9	1	NM_138401.4	ENSP00000324810.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Sep 21, 2023

The c.97T>G (p.C33G) alteration is located in exon 2 (coding exon 2) of the MVB12A gene. This alteration results from a T to G substitution at nucleotide position 97, causing the cysteine (C) at amino acid position 33 to be replaced by a glycine (G). 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	0.096
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.011	T;T;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0040	B;.;.;B
Vest4		0.49
MutPred		0.44		Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);
MVP		0.39
MPC		0.29
ClinPred		0.097	T
GERP RS		2.5
Varity_R		0.25
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17531128;