rs1297882491

Variant names:

• chr19-17420176-G-A
• rs1297882491
• NM_138401.4:c.41G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138401.4(MVB12A):​c.41G>A​(p.Gly14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,425,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: MVB12A NM_138401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138401.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12A	NM_138401.4	MANE Select	c.41G>A	p.Gly14Asp	missense	Exon 1 of 9	NP_612410.1	Q96EY5-1
	MVB12A	NM_001304547.2		c.-186-137G>A		intron	N/A	NP_001291476.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12A	ENST00000317040.12	TSL:1 MANE Select	c.41G>A	p.Gly14Asp	missense	Exon 1 of 9	ENSP00000324810.6	Q96EY5-1
	MVB12A	ENST00000529939.5	TSL:3	c.41G>A	p.Gly14Asp	missense	Exon 1 of 8	ENSP00000432526.1	E9PQA6
	MVB12A	ENST00000875213.1		c.41G>A	p.Gly14Asp	missense	Exon 1 of 8	ENSP00000545272.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152142 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 60098 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1273714 Hom.: 0 Cov.: 32 AF XY: 0.00000162 AC XY: 1 AN XY: 618432

African (AFR) AF: 0.0000384 AC: 1 AN: 26026

American (AMR) AF: 0.00 AC: 0 AN: 16178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18102

East Asian (EAS) AF: 0.00 AC: 0 AN: 31188

South Asian (SAS) AF: 0.00 AC: 0 AN: 59382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029494

Other (OTH) AF: 0.0000190 AC: 1 AN: 52610

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152142 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.78	P
Vest4		0.63
MutPred		0.68		Loss of sheet (P = 0.0315)
MVP		0.54
MPC		0.67
ClinPred		0.91	D
GERP RS		2.8
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.60
gMVP		0.78
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1297882491; hg19: chr19-17530985;