chr10-133240130-T-C

Position:

• chr10-133240130-T-C

Variant summary

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

The NM_014468.4(VENTX):​c.601T>C​(p.Ser201Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VENTX NM_014468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0260

Genes affected

VENTX (HGNC:13639): (VENT homeobox) This gene encodes a member of the Vent family of homeodomain proteins. The encoded protein may function as a transcriptional repressor and be involved in mesodermal patterning and hemopoietic stem cell maintenance. Multiple pseudogenes exist for this gene. A transcribed pseudogene located on chromosome X may lead to antigen production in certain melanomas. [provided by RefSeq, Jul 2008]

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=0.07092741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VENTX	NM_014468.4	c.601T>C	p.Ser201Pro	missense_variant	3/3	ENST00000325980.10	NP_055283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VENTX	ENST00000325980.10	c.601T>C	p.Ser201Pro	missense_variant	3/3	1	NM_014468.4	ENSP00000357556.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Nov 07, 2022

The c.601T>C (p.S201P) alteration is located in exon 3 (coding exon 3) of the VENTX gene. This alteration results from a T to C substitution at nucleotide position 601, causing the serine (S) at amino acid position 201 to be replaced by a proline (P). 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	0.082
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.098
Sift	Benign	0.24	T
Sift4G	Benign	0.27	T
Polyphen		0.027	B
Vest4		0.16
MutPred		0.28		Gain of glycosylation at P198 (P = 0.1373);
MVP		0.39
MPC		0.12
ClinPred		0.050	T
GERP RS		1.7
Varity_R		0.067
gMVP		0.19

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: rs1845912423; hg19: chr10-135053634;