Genetic Variant ST7:p.Ala4Val (chr7-116953551-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001369598.1(ST7):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,412,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ST7
NM_001369598.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

ST7 (HGNC:11351): (suppression of tumorigenicity 7) The gene for this product maps to a region on chromosome 7 identified as an autism-susceptibility locus. Mutation screening of the entire coding region in autistic individuals failed to identify phenotype-specific variants, suggesting that coding mutations for this gene are unlikely to be involved in the etiology of autism. The function of this gene product has not been determined. Transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

ST7 links:

ST7-AS1 (HGNC:16000): (ST7 antisense RNA 1)

ST7-AS1 links:

ENSG00000277583 (HGNC:):

ENSG00000277583 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11976385).

BS2

High AC in GnomAdExome4 at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST7	NM_001369598.1 link	c.11C>T	p.Ala4Val	missense_variant	Exon 1 of 16	ENST00000323984.8	NP_001356527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST7	ENST00000323984.8 link	c.11C>T	p.Ala4Val	missense_variant	Exon 1 of 16	5	NM_001369598.1	ENSP00000325673.3		H7BXS2

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000404

AC:

AN:

198078

Hom.:

AF XY:

0.0000184

AC XY:

AN XY:

108924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000155

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000219

Gnomad OTH exome

AF:

0.000460

GnomAD4 exome

AF:

0.0000309

AC:

AN:

1263262

Hom.:

Cov.:

AF XY:

0.0000335

AC XY:

AN XY:

627458

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000239

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:

0.0000252

Gnomad4 OTH exome

AF:

0.0000824

GnomAD4 genome

AF:

0.0000269

AC:

AN:

148924

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72636

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the ST7 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.010

T;T;.;.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.88

D;D;D;D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L;L;.;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.46

N;N;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.057

T;D;T;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.96, 0.98

.;D;D;.;.;.

Vest4

0.22

MutPred

0.13

Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);

MVP

0.043

MPC

0.13

ClinPred

0.28

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over