chr17-18789405-C-T

Variant names:

• chr17-18789405-C-T
• rs201133102
• ENST00000476139.5:c.-128C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001316919.1(TVP23B):​c.-128C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: TVP23B NM_001316919.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.258
• Publications: 1 publications found

Genes affected

TVP23B (HGNC:20399): (trans-golgi network vesicle protein 23 homolog B) Predicted to be involved in protein secretion and vesicle-mediated transport. Predicted to be integral component of membrane. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023415118).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316919.1. 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
	TVP23B	NM_016078.6	MANE Select	c.65C>T	p.Thr22Met	missense	Exon 2 of 7	NP_057162.4	Q9NYZ1
	TVP23B	NM_001316919.1		c.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001303848.1	J3QL63
	TVP23B	NM_001316920.1		c.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001303849.1	Q9NYZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TVP23B	ENST00000476139.5	TSL:1	c.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000463400.2	J3QL63
	TVP23B	ENST00000307767.13	TSL:1 MANE Select	c.65C>T	p.Thr22Met	missense	Exon 2 of 7	ENSP00000305654.8	Q9NYZ1
	TVP23B	ENST00000574226.5	TSL:1	c.65C>T	p.Thr22Met	missense	Exon 2 of 6	ENSP00000462334.1	J3KS67

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152060 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000171 AC: 43 AN: 251166 AF XY: 0.000177

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000249 AC: 364 AN: 1461660 Hom.: 0 Cov.: 30 AF XY: 0.000257 AC XY: 187 AN XY: 727140

African (AFR) AF: 0.000418 AC: 14 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.000296 AC: 329 AN: 1111834

Other (OTH) AF: 0.000149 AC: 9 AN: 60378

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.000296 AC XY: 22 AN XY: 74404

African (AFR) AF: 0.000434 AC: 18 AN: 41510

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000947 AC: 1 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000300 Hom.: 0

Bravo AF: 0.000291

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Benign	0.76
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
PhyloP100		0.26
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.012
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.31	B
Vest4		0.12
MVP		0.030
MPC		0.046
ClinPred		0.024	T
GERP RS		2.8
PromoterAI		0.057	Neutral
Varity_R		0.033
gMVP		0.22
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs201133102; hg19: chr17-18692718; COSMIC: COSV57060173;