16-10773346-A-G

Variant names:

• chr16-10773346-A-G
• rs1340344264
• NM_001079512.4:c.420T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001079512.4(TVP23A):​c.420T>C​(p.Phe140Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TVP23A NM_001079512.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.631 with no splicing effect.

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.420T>C	p.Phe140Phe	synonymous	Exon 5 of 8	NP_001072980.1	A6NH52-1
	TVP23A	NM_001318873.2		c.228T>C	p.Phe76Phe	synonymous	Exon 5 of 8	NP_001305802.1
	TVP23A	NR_134901.2		n.791T>C		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TVP23A	ENST00000299866.13	TSL:2 MANE Select	c.420T>C	p.Phe140Phe	synonymous	Exon 5 of 8	ENSP00000299866.8	A6NH52-1
	TVP23A	ENST00000572428.5	TSL:1	c.231T>C	p.Phe77Phe	synonymous	Exon 3 of 6	ENSP00000460822.1	I3L3Y3
	TVP23A	ENST00000456096.6	TSL:1	n.345T>C		non_coding_transcript_exon	Exon 5 of 9	ENSP00000411972.2	A6NH52-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440372 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715896

⚠️ 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: 32654

American (AMR) AF: 0.00 AC: 0 AN: 41438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25538

East Asian (EAS) AF: 0.00 AC: 0 AN: 38938

South Asian (SAS) AF: 0.00 AC: 0 AN: 82380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101748

Other (OTH) AF: 0.00 AC: 0 AN: 59396

⚠️ 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.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		0.63
PromoterAI		-0.011	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1340344264; hg19: chr16-10867203;