rs569991781

Variant names:

• chr16-10770307-G-A
• rs569991781
• NM_001079512.4:c.607C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-10770307-G-A
• chr16-10770307-G-C
• chr16-10770307-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001079512.4(TVP23A):​c.607C>T​(p.Pro203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.1e-7 (0 hom.)
• Consequence: TVP23A NM_001079512.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14199045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TVP23A	NM_001079512.4	c.607C>T	p.Pro203Ser	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.607C>T	p.Pro203Ser	missense_variant	Exon 7 of 8	2	NM_001079512.4	ENSP00000299866.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398846 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690034

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;T;.
Eigen	Benign	-0.042
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.73	T;T;.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	.;.;N;.
REVEL	Benign	0.087
Sift	Benign	0.087	.;.;T;.
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.61	P;.;P;.
Vest4		0.30
MutPred		0.32		Gain of glycosylation at P203 (P = 0.0251);.;Gain of glycosylation at P203 (P = 0.0251);.;
MVP		0.12
MPC		0.045
ClinPred		0.50	D
GERP RS		5.4
Varity_R		0.078
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs569991781; hg19: chr16-10864164;