X-136548778-C-T

Position:

• chrX-136548778-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016267.4(VGLL1):​c.404C>T​(p.Ser135Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: VGLL1 NM_016267.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19485009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL1	NM_016267.4	c.404C>T	p.Ser135Phe	missense_variant	3/5	ENST00000370634.8	NP_057351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL1	ENST00000370634.8	c.404C>T	p.Ser135Phe	missense_variant	3/5	1	NM_016267.4	ENSP00000359668	P1
VGLL1	ENST00000440515.5	c.299C>T	p.Ser100Phe	missense_variant	2/4	3		ENSP00000398360
VGLL1	ENST00000456412.1	c.41-1990C>T		intron_variant		3		ENSP00000388868

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

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

Oct 06, 2021

The c.404C>T (p.S135F) alteration is located in exon 3 (coding exon 2) of the VGLL1 gene. This alteration results from a C to T substitution at nucleotide position 404, causing the serine (S) at amino acid position 135 to be replaced by a phenylalanine (F). 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	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.099
Sift	Benign	0.057	T
Sift4G	Benign	0.32	T
Polyphen		0.36	B
Vest4		0.40
MutPred		0.23		Loss of disorder (P = 0.0116);
MVP		0.36
MPC		0.59
ClinPred		0.32	T
GERP RS		4.9
Varity_R		0.15
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs1369902771; hg19: chrX-135630937;