3-86968857-C-T

Position:

• chr3-86968857-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016206.4(VGLL3):​c.670G>A​(p.Asp224Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VGLL3 NM_016206.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

Genes affected

VGLL3 (HGNC:24327): (vestigial like family member 3) Predicted to enable protein C-terminus binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL3	NM_016206.4	c.670G>A	p.Asp224Asn	missense_variant	3/4	ENST00000398399.7	NP_057290.2
VGLL3	NM_001320493.2	c.670G>A	p.Asp224Asn	missense_variant	3/4		NP_001307422.1
VGLL3	NM_001320494.2	c.511G>A	p.Asp171Asn	missense_variant	3/4		NP_001307423.1
VGLL3	XM_006713138.5	c.667G>A	p.Asp223Asn	missense_variant	3/4		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000398399.7	c.670G>A	p.Asp224Asn	missense_variant	3/4	1	NM_016206.4	ENSP00000381436	P1
VGLL3	ENST00000383698.3	c.670G>A	p.Asp224Asn	missense_variant	3/4	1		ENSP00000373199
VGLL3	ENST00000494229.1	c.472G>A	p.Asp158Asn	missense_variant	3/3	3		ENSP00000419115

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.670G>A (p.D224N) alteration is located in exon 3 (coding exon 3) of the VGLL3 gene. This alteration results from a G to A substitution at nucleotide position 670, causing the aspartic acid (D) at amino acid position 224 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.032	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.31	T;T
Polyphen		0.79	P;.
Vest4		0.63
MutPred		0.28		Gain of glycosylation at Y219 (P = 4e-04);Gain of glycosylation at Y219 (P = 4e-04);
MVP		0.46
MPC		0.23
ClinPred		0.63	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-87018007;