20-37944073-C-T

Variant names:

• chr20-37944073-C-T
• rs766041079
• NM_080607.3:c.435C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_080607.3(VSTM2L):​c.435C>T​(p.Ile145Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,598 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: 29)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VSTM2L NM_080607.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 0 publications found

Genes affected

VSTM2L (HGNC:16096): (V-set and transmembrane domain containing 2 like) Predicted to enable cell-cell adhesion mediator activity. Involved in negative regulation of neuron apoptotic process. Located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.0408614).
• BP7: Synonymous conserved (PhyloP=0.888 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080607.3. 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
	VSTM2L	NM_080607.3	MANE Select	c.435C>T	p.Ile145Ile	synonymous	Exon 4 of 4	NP_542174.1	Q96N03-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2L	ENST00000373461.9	TSL:1 MANE Select	c.435C>T	p.Ile145Ile	synonymous	Exon 4 of 4	ENSP00000362560.4	Q96N03-1
	VSTM2L	ENST00000373459.4	TSL:3	c.214C>T	p.Arg72*	stop_gained	Exon 2 of 2	ENSP00000362558.4	Q96N03-3
	VSTM2L	ENST00000954389.1		c.423C>T	p.Ile141Ile	synonymous	Exon 4 of 4	ENSP00000624448.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460598 Hom.: 0 Cov.: 45 AF XY: 0.00000138 AC XY: 1 AN XY: 726470

⚠️ 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: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111290

Other (OTH) AF: 0.00 AC: 0 AN: 60294

⚠️ 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.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Uncertain	1.0
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.78	D
PhyloP100		0.89
Vest4		0.055
GERP RS		3.2
Mutation Taster		=77/123	disease causing

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: rs766041079; hg19: chr20-36572475; COSMIC: COSV104683077;