rs150457252

Variant names:

• chr19-17422395-C-A
• rs150457252
• NM_138401.4:c.350C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-17422395-C-A
• chr19-17422395-C-G
• chr19-17422395-C-T

Variant summary

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

The NM_138401.4(MVB12A):​c.350C>A​(p.Thr117Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MVB12A NM_138401.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12A	NM_138401.4	c.350C>A	p.Thr117Lys	missense_variant	Exon 4 of 9	ENST00000317040.12	NP_612410.1
MVB12A	NM_001304547.2	c.74C>A	p.Thr25Lys	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.350C>A	p.Thr117Lys	missense_variant	Exon 4 of 9	1	NM_138401.4	ENSP00000324810.6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 32

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

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74262

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.9
DANN	Benign	0.92
DEOGEN2	Benign	0.084	T;T;T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.68	.;T;.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	.;.;L;.;L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.4	D;.;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.014	D;.;D;T;D
Sift4G	Uncertain	0.059	T;T;D;D;D
Polyphen		0.62	.;.;P;.;P
Vest4		0.60, 0.60
MutPred		0.69		.;.;Gain of ubiquitination at T117 (P = 0.0247);Gain of ubiquitination at T117 (P = 0.0247);Gain of ubiquitination at T117 (P = 0.0247);
MVP		0.28
MPC		0.45
ClinPred		0.81	D
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs150457252; hg19: chr19-17533204;