chr19-17422395-C-G

Variant names:

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

Variant summary

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

The NM_138401.4(MVB12A):​c.350C>G​(p.Thr117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,512 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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>G	p.Thr117Arg	missense_variant	Exon 4 of 9	ENST00000317040.12	NP_612410.1
MVB12A	NM_001304547.2	c.74C>G	p.Thr25Arg	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>G	p.Thr117Arg	missense_variant	Exon 4 of 9	1	NM_138401.4	ENSP00000324810.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461512 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.069	T;T;T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.72	.;T;.;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	.;.;L;.;L
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.5	D;.;D;N;D
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D;.;D;D;D
Sift4G	Uncertain	0.038	D;D;D;D;D
Polyphen		0.62	.;.;P;.;P
Vest4		0.58, 0.60
MutPred		0.69		.;.;Gain of MoRF binding (P = 0.0274);Gain of MoRF binding (P = 0.0274);Gain of MoRF binding (P = 0.0274);
MVP		0.40
MPC		0.55
ClinPred		0.80	D
GERP RS		-2.3
Varity_R		0.22
gMVP		0.53

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: chr19-17533204;