16-4381021-A-G

Variant names:

• chr16-4381021-A-G
• NM_138440.3:c.144A>G
• VASN p.Arg48Arg

Variant summary

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

The NM_138440.3(VASN):​c.144A>G​(p.Arg48Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: VASN NM_138440.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.66
• Publications: 0 publications found

Genes affected

VASN (HGNC:18517): (vasorin) Enables transforming growth factor beta binding activity. Involved in negative regulation of epithelial to mesenchymal transition and negative regulation of transforming growth factor beta receptor signaling pathway. Located in cell surface and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CORO7 (HGNC:26161): (coronin 7) This gene encodes a member of the coronin protein family. However, unlike other coronin proteins, it is not an actin-binding protein but rather functions as an F-actin regulator directing anterograde Golgi to endosome transport. The encoded protein has two tandem WD-40 domain repeats and localizes to the trans-Golgi network. The protein undergoes K33-linked polyubiquitination via an E3 ligase complex. It is thought to play an essential role in maintenance of Golgi apparatus morphology. Alternative splicing results in multiple transcripts variants; some of which form read-through transcripts with a neighboring gene. [provided by RefSeq, Dec 2016]

CORO7-PAM16 (HGNC:44424): (CORO7-PAM16 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CORO7 (coronin 7) and PAM16 (presequence translocase-associated motor 16) genes on chromosome 16. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2011]

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=-0.91).
• BP7: Synonymous conserved (PhyloP=-4.66 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138440.3. 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
	VASN	NM_138440.3	MANE Select	c.144A>G	p.Arg48Arg	synonymous	Exon 2 of 2	NP_612449.2	Q6EMK4
	CORO7	NM_024535.5	MANE Select	c.785+6965T>C		intron	N/A	NP_078811.3	P57737-1
	CORO7-PAM16	NM_001201479.2		c.785+6965T>C		intron	N/A	NP_001188408.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VASN	ENST00000304735.4	TSL:1 MANE Select	c.144A>G	p.Arg48Arg	synonymous	Exon 2 of 2	ENSP00000306864.3	Q6EMK4
	CORO7	ENST00000251166.9	TSL:1 MANE Select	c.785+6965T>C		intron	N/A	ENSP00000251166.4	P57737-1
	CORO7-PAM16	ENST00000572467.5	TSL:2	c.785+6965T>C		intron	N/A	ENSP00000460885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.45
PhyloP100		-4.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-4431022;