16-10770298-C-T

Variant names:

• chr16-10770298-C-T
• rs371043030
• NM_001079512.4:c.616G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001079512.4(TVP23A):​c.616G>A​(p.Glu206Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,551,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: TVP23A NM_001079512.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.118

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.015962392).
• BP6: Variant 16-10770298-C-T is Benign according to our data. Variant chr16-10770298-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2343514.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-10770298-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TVP23A	NM_001079512.4	c.616G>A	p.Glu206Lys	missense_variant	Exon 7 of 8	ENST00000299866.13	NP_001072980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TVP23A	ENST00000299866.13	c.616G>A	p.Glu206Lys	missense_variant	Exon 7 of 8	2	NM_001079512.4	ENSP00000299866.8

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000156 AC: 24 AN: 154174 Hom.: 0 AF XY: 0.000196 AC XY: 16 AN XY: 81722

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000884

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.000930

GnomAD4 exome AF: 0.000256 AC: 358 AN: 1398712 Hom.: 1 Cov.: 31 AF XY: 0.000268 AC XY: 185 AN XY: 689980

Gnomad4 AFR exome AF: 0.000476

Gnomad4 AMR exome AF: 0.0000281

Gnomad4 ASJ exome AF: 0.000358

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000885

Gnomad4 FIN exome AF: 0.0000406

Gnomad4 NFE exome AF: 0.000233

Gnomad4 OTH exome AF: 0.000466

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74486

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000824 Hom.: 0

Bravo AF: 0.000125

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000130 AC: 1

ExAC AF: 0.0000993 AC: 9

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 05, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.74
DEOGEN2	Benign	0.012	T;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.60	T;T;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.016	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N;.;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.60	.;.;N;.
REVEL	Benign	0.018
Sift	Benign	0.20	.;.;T;.
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0020	B;.;B;.
Vest4		0.17
MVP		0.030
MPC		0.040
ClinPred		0.0059	T
GERP RS		0.17
Varity_R		0.045
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs371043030; hg19: chr16-10864155;