16-10770298-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001079512.4(TVP23A):​c.616G>C​(p.Glu206Gln) 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 1,398,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E206K) has been classified as Likely benign.

• 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: 0.118
• Publications: 2 publications found

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.015088052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079512.4. 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
	TVP23A	NM_001079512.4	MANE Select	c.616G>C	p.Glu206Gln	missense	Exon 7 of 8	NP_001072980.1	A6NH52-1
	TVP23A	NM_001318873.2		c.424G>C	p.Glu142Gln	missense	Exon 7 of 8	NP_001305802.1
	TVP23A	NR_134901.2		n.987G>C		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TVP23A	ENST00000299866.13	TSL:2 MANE Select	c.616G>C	p.Glu206Gln	missense	Exon 7 of 8	ENSP00000299866.8	A6NH52-1
	TVP23A	ENST00000572428.5	TSL:1	c.427G>C	p.Glu143Gln	missense	Exon 5 of 6	ENSP00000460822.1	I3L3Y3
	TVP23A	ENST00000456096.6	TSL:1	n.541G>C		non_coding_transcript_exon	Exon 7 of 9	ENSP00000411972.2	A6NH52-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000649 AC: 1 AN: 154174 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000933

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398712 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689980

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31498

American (AMR) AF: 0.00 AC: 0 AN: 35574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35572

South Asian (SAS) AF: 0.00 AC: 0 AN: 79070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078872

Other (OTH) AF: 0.0000172 AC: 1 AN: 57996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000110 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.12
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.024
Sift	Benign	0.041	D
Sift4G	Benign	0.28	T
Polyphen		0.36	B
Vest4		0.17
MutPred		0.14		Gain of sheet (P = 0.0827)
MVP		0.014
MPC		0.050
ClinPred		0.022	T
GERP RS		0.17
Varity_R		0.071
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs371043030; hg19: chr16-10864155;