NM_016267.4:c.454G>T

Variant names:

• chrX-136548828-G-T
• rs769583709
• NM_016267.4:c.454G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016267.4(VGLL1):​c.454G>T​(p.Ala152Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,252 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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. A152T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: VGLL1 NM_016267.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 1 publications found

Genes affected

VGLL1 (HGNC:20985): (vestigial like family member 1) The protein encoded by this gene binds proteins of the TEA domain family of transcription factors (TEFs) through the Vg (vestigial) homology region found in its N-terminus. It may thus function as a specific coactivator for the mammalian TEFs. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034128517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGLL1	NM_016267.4	c.454G>T	p.Ala152Ser	missense_variant	Exon 3 of 5	ENST00000370634.8	NP_057351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGLL1	ENST00000370634.8	c.454G>T	p.Ala152Ser	missense_variant	Exon 3 of 5	1	NM_016267.4	ENSP00000359668.3
VGLL1	ENST00000440515.5	c.346G>T	p.Ala116Ser	missense_variant	Exon 2 of 4	3		ENSP00000398360.1
VGLL1	ENST00000456412.1	c.41-1940G>T		intron_variant	Intron 1 of 2	3		ENSP00000388868.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098252 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363606

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40517

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842149

Other (OTH) AF: 0.00 AC: 0 AN: 46098

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.011
DANN	Benign	0.41
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.41
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.039
Sift	Benign	0.77	T
Sift4G	Benign	0.84	T
Polyphen		0.013	B
Vest4		0.067
MutPred		0.050		Gain of phosphorylation at A152 (P = 0.0244);
MVP		0.12
MPC		0.37
ClinPred		0.026	T
GERP RS		-4.7
Varity_R		0.043
gMVP		0.063
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs769583709; hg19: chrX-135630987;