NM_001079512.4:c.362C>A

Variant names:

• chr16-10773404-G-T
• NM_001079512.4:c.362C>A

Variant summary

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

The NM_001079512.4(TVP23A):​c.362C>A​(p.Ala121Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TVP23A NM_001079512.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.72

Genes affected

TVP23A (HGNC:20398): (trans-golgi network vesicle protein 23 homolog A) This gene encodes a membrane protein associated with the Golgi apparatus, which plays a crucial role in intracellular vesicular transport. The encoded protein is likely associated with the late (trans) Golgi compartments, which are involved in the delivery of secretory and membrane proteins to the endosome, lysosome or the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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
TVP23A	NM_001079512.4	c.362C>A	p.Ala121Glu	missense_variant	Exon 5 of 8	ENST00000299866.13	NP_001072980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TVP23A	ENST00000299866.13	c.362C>A	p.Ala121Glu	missense_variant	Exon 5 of 8	2	NM_001079512.4	ENSP00000299866.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362C>A (p.A121E) alteration is located in exon 5 (coding exon 5) of the TVP23A gene. This alteration results from a C to A substitution at nucleotide position 362, causing the alanine (A) at amino acid position 121 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.087	T;.;T;.
Eigen	Benign	0.054
Eigen_PC	Benign	0.047
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;.;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M;.;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	.;.;N;.
REVEL	Benign	0.28
Sift	Benign	0.041	.;.;D;.
Sift4G	Uncertain	0.025	D;T;D;D
Polyphen		0.63	P;.;P;.
Vest4		0.31
MutPred		0.62		Gain of disorder (P = 0.0525);.;Gain of disorder (P = 0.0525);.;
MVP		0.18
MPC		0.075
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.48
gMVP		0.80

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: chr16-10867261;