14-74357336-C-G

Variant names:

• chr14-74357336-C-G
• rs762560330
• NM_018228.3:c.553C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018228.3(VRTN):​c.553C>G​(p.Arg185Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. R185W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VRTN NM_018228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 0 publications found

Genes affected

VRTN (HGNC:20223): (vertebrae development associated) Predicted to enable sequence-specific DNA binding activity and transposase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31558514).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018228.3. 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
	VRTN	NM_018228.3	MANE Select	c.553C>G	p.Arg185Gly	missense	Exon 2 of 2	NP_060698.2	Q9H8Y1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRTN	ENST00000256362.5	TSL:1 MANE Select	c.553C>G	p.Arg185Gly	missense	Exon 2 of 2	ENSP00000256362.4	Q9H8Y1
	VRTN	ENST00000925859.1		c.553C>G	p.Arg185Gly	missense	Exon 2 of 2	ENSP00000595918.1
	VRTN	ENST00000925860.1		c.553C>G	p.Arg185Gly	missense	Exon 3 of 3	ENSP00000595919.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Benign	0.43	T
Sift4G	Benign	0.38	T
Polyphen		0.47	P
Vest4		0.52
MutPred		0.45		Gain of sheet (P = 0.0085)
MVP		0.082
MPC		1.1
ClinPred		0.38	T
GERP RS		3.2
Varity_R		0.12
gMVP		0.97
Mutation Taster		=94/6	polymorphism

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: rs762560330; hg19: chr14-74824039;