chr6-142170374-A-T

Variant names:

• chr6-142170374-A-T
• rs1775005744
• NM_016485.5:c.364A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016485.5(VTA1):​c.364A>T​(p.Ser122Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S122G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VTA1 NM_016485.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.64
• Publications: 0 publications found

Genes affected

VTA1 (HGNC:20954): (vesicle trafficking 1) C6ORF55 encodes a protein involved in trafficking of the multivesicular body, an endosomal compartment involved in sorting membrane proteins for degradation in lysosomes (Ward et al., 2005 [PubMed 15644320]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016485.5. 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
	VTA1	NM_016485.5	MANE Select	c.364A>T	p.Ser122Cys	missense	Exon 4 of 8	NP_057569.2
	VTA1	NM_001286371.2		c.364A>T	p.Ser122Cys	missense	Exon 4 of 7	NP_001273300.1	A0A087WY55
	VTA1	NM_001286372.2		c.190A>T	p.Ser64Cys	missense	Exon 3 of 6	NP_001273301.1	Q9NP79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTA1	ENST00000367630.9	TSL:1 MANE Select	c.364A>T	p.Ser122Cys	missense	Exon 4 of 8	ENSP00000356602.3	Q9NP79-1
	VTA1	ENST00000934453.1		c.358A>T	p.Ser120Cys	missense	Exon 4 of 8	ENSP00000604512.1
	VTA1	ENST00000890565.1		c.364A>T	p.Ser122Cys	missense	Exon 4 of 8	ENSP00000560624.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		8.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.47
Sift	Benign	0.047	D
Sift4G	Uncertain	0.057	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.73		Gain of catalytic residue at L123 (P = 0.0117)
MVP		0.80
MPC		0.30
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.57
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1775005744; hg19: chr6-142491511;