chr3-11558818-G-T

Position:

• chr3-11558818-G-T

Variant summary

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

The NM_001128219.3(VGLL4):​c.629C>A​(p.Thr210Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VGLL4 NM_001128219.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46

Genes affected

VGLL4 (HGNC:28966): (vestigial like family member 4) Predicted to enable transcription coactivator binding activity. Involved in negative regulation of Wnt signaling pathway; negative regulation of cell growth; and negative regulation of hippo signaling. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ATG7 (HGNC:):

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=0.22420505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGLL4	NM_001128219.3	c.629C>A	p.Thr210Asn	missense_variant	5/5	ENST00000430365.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGLL4	ENST00000430365.7	c.629C>A	p.Thr210Asn	missense_variant	5/5	2	NM_001128219.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458656 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 724964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T;T;.;.;.;T;T
Eigen	Benign	-0.0026
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.58	D;D;D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.86	N;N;N;N;N;.;N
REVEL	Benign	0.074
Sift	Benign	0.14	T;T;T;T;T;.;D
Sift4G	Benign	0.29	T;T;T;.;T;T;.
Polyphen		0.50, 0.22, 0.38	.;.;P;B;B;.;.
Vest4		0.12
MutPred		0.14		.;.;.;.;Loss of glycosylation at T210 (P = 0.0025);.;.;
MVP		0.17
MPC		0.38
ClinPred		0.89	D
GERP RS		4.7
gMVP		0.31

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: rs1385753534; hg19: chr3-11600292;