rs371492135

Variant names:

• chr19-17420344-G-A
• rs371492135
• NM_138401.4:c.122G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-17420344-G-A
• chr19-17420344-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138401.4(MVB12A):​c.122G>A​(p.Ser41Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S41T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MVB12A NM_138401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.108
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06583843).

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.122G>A	p.Ser41Asn	missense	Exon 2 of 9	NP_612410.1	Q96EY5-1
	MVB12A	NM_001304547.2		c.-155G>A		5_prime_UTR	Exon 3 of 10	NP_001291476.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12A	ENST00000317040.12	TSL:1 MANE Select	c.122G>A	p.Ser41Asn	missense	Exon 2 of 9	ENSP00000324810.6	Q96EY5-1
	MVB12A	ENST00000529939.5	TSL:3	c.122G>A	p.Ser41Asn	missense	Exon 2 of 8	ENSP00000432526.1	E9PQA6
	MVB12A	ENST00000875213.1		c.122G>A	p.Ser41Asn	missense	Exon 2 of 8	ENSP00000545272.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250182 AF XY: 0.00000739

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460902 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726774

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111640

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

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	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.040	N
PhyloP100		0.11
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.073
Sift	Benign	0.87	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.45		Loss of phosphorylation at S41 (P = 0.0447)
MVP		0.26
MPC		0.18
ClinPred		0.059	T
GERP RS		2.5
PromoterAI		-0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.15
Mutation Taster		=75/25	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: rs371492135; hg19: chr19-17531153;