19-17423556-A-G

Variant names:

• chr19-17423556-A-G
• NM_138401.4:c.472A>G

Variant summary

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

The NM_138401.4(MVB12A):​c.472A>G​(p.Lys158Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MVB12A NM_138401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

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]

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=0.3204107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12A	NM_138401.4	c.472A>G	p.Lys158Glu	missense_variant	Exon 5 of 9	ENST00000317040.12	NP_612410.1
MVB12A	NM_001304547.2	c.196A>G	p.Lys66Glu	missense_variant	Exon 6 of 10		NP_001291476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVB12A	ENST00000317040.12	c.472A>G	p.Lys158Glu	missense_variant	Exon 5 of 9	1	NM_138401.4	ENSP00000324810.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.472A>G (p.K158E) alteration is located in exon 5 (coding exon 5) of the MVB12A gene. This alteration results from a A to G substitution at nucleotide position 472, causing the lysine (K) at amino acid position 158 to be replaced by a glutamic acid (E). 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	0.20
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;.;T;T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.66	.;T;T;.;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.4	.;.;.;M;.;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.0	N;N;.;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.012	D;D;.;D;D;D
Sift4G	Uncertain	0.023	D;T;D;T;D;T
Polyphen		0.94	.;.;.;P;.;P
Vest4		0.48, 0.49
MutPred		0.48		.;.;.;Loss of methylation at K158 (P = 0.0012);Loss of methylation at K158 (P = 0.0012);Loss of methylation at K158 (P = 0.0012);
MVP		0.60
MPC		0.65
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.26
gMVP		0.54

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: chr19-17534365;