16-10770298-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. 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. 16/23 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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• 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

GnomAD2 exomes AF: 0.000156 AC: 24 AN: 154174 AF XY: 0.000196

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 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 AC: 15 AN: 31498

Gnomad4 AMR exome AF: 0.0000281 AC: 1 AN: 35574

Gnomad4 ASJ exome AF: 0.000358 AC: 9 AN: 25158

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35572

Gnomad4 SAS exome AF: 0.0000885 AC: 7 AN: 79070

Gnomad4 FIN exome AF: 0.0000406 AC: 2 AN: 49294

Gnomad4 NFE exome AF: 0.000233 AC: 251 AN: 1078872

Gnomad4 Remaining exome AF: 0.000466 AC: 27 AN: 57996

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 AC: 0.000144349 AN: 0.000144349

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.000576 AC: 0.000576037 AN: 0.000576037

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207211 AN: 0.000207211

Gnomad4 FIN AF: 0.0000942 AC: 0.0000941797 AN: 0.0000941797

Gnomad4 NFE AF: 0.000162 AC: 0.000161679 AN: 0.000161679

Gnomad4 OTH AF: 0.000473 AC: 0.000473485 AN: 0.000473485

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
Mutation Taster		=95/5	polymorphism

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;