NM_000638.4:c.1395C>T

Variant names:

• chr17-28367411-G-A
• rs150241335
• NM_000638.4:c.1395C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000638.4(VTN):​c.1395C>T​(p.Ile465Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,612,412 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: VTN NM_000638.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.645
• Publications: 0 publications found

Genes affected

VTN (HGNC:12724): (vitronectin) The protein encoded by this gene functions in part as an adhesive glycoprotein. Differential expression of this protein can promote either cell adhesion or migration as it links cells to the extracellular matrix through a variety of ligands. These ligands include integrins, plasminogen activator inhibitor-1, and urokinase plasminogen activator receptor. This secreted protein can be present in the plasma as a monomer or dimer and forms a multimer in the extracellular matrix of several tissues. This protein also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpin serine protease inhibitors. This protein can also promote extracellular matrix degradation and thus plays a role in tumorigenesis. It is involved in a variety of other biological processes such as the regulation of the coagulation pathway, wound healing, and tissue remodeling. The heparin-binding domain of this protein give it anti-microbial properties. It is also a lipid binding protein that forms a principal component of high density lipoprotein. [provided by RefSeq, Aug 2020]

ENSG00000273171 (HGNC:):

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 17-28367411-G-A is Benign according to our data. Variant chr17-28367411-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.
• BS2: High AC in GnomAd4 at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTN	NM_000638.4	c.1395C>T	p.Ile465Ile	synonymous_variant	Exon 8 of 8	ENST00000226218.9	NP_000629.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTN	ENST00000226218.9	c.1395C>T	p.Ile465Ile	synonymous_variant	Exon 8 of 8	1	NM_000638.4	ENSP00000226218.4
ENSG00000273171	ENST00000555059.2	c.329+40C>T		intron_variant	Intron 2 of 3	4		ENSP00000452347.3
SARM1	ENST00000379061.8	n.170+2246G>A		intron_variant	Intron 2 of 10	2
ENSG00000258924	ENST00000591482.1	n.555+6564G>A		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 248882 AF XY: 0.0000668

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.0000589

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000527 AC: 77 AN: 1460072 Hom.: 0 Cov.: 30 AF XY: 0.0000441 AC XY: 32 AN XY: 726368

African (AFR) AF: 0.00129 AC: 43 AN: 33366

American (AMR) AF: 0.0000906 AC: 4 AN: 44170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111510

Other (OTH) AF: 0.000133 AC: 8 AN: 60298

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74496

African (AFR) AF: 0.00127 AC: 53 AN: 41574

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000404

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.17
DANN	Benign	0.88
PhyloP100		-0.65
Mutation Taster		=97/3	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: rs150241335; hg19: chr17-26694432; COSMIC: COSV52647022; COSMIC: COSV52647022;