7-117130604-C-G

Position:

chr7-117130604-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_001369598.1(ST7):c.563C>G(p.Ala188Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000561 in 1,605,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ST7
NM_001369598.1 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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-AS2 (HGNC:16044): (ST7 antisense RNA 2)

ST7-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ST7. . Gene score misZ 3.3795 (greater than the threshold 3.09). Trascript score misZ 3.691 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy.

BP4

Computational evidence support a benign effect (MetaRNN=0.3133558).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST7	NM_001369598.1 linkuse as main transcript	c.563C>G	p.Ala188Gly	missense_variant, splice_region_variant	5/16	ENST00000323984.8	NP_001356527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST7	ENST00000323984.8 linkuse as main transcript	c.563C>G	p.Ala188Gly	missense_variant, splice_region_variant	5/16	5	NM_001369598.1	ENSP00000325673
ST7-AS2	ENST00000432541.5 linkuse as main transcript	n.250+13563G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246624

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1453644

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723362

show subpopulations

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:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151860

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000737

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.563C>G (p.A188G) alteration is located in exon 5 (coding exon 5) of the ST7 gene. This alteration results from a C to G substitution at nucleotide position 563, causing the alanine (A) at amino acid position 188 to be replaced by a glycine (G). 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

0.30

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;.;.;T;.;T;T;.;.;T;T;.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.31

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

.;L;L;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T;T;T;.;T;T;T;T;T

Polyphen

0.24, 0.40, 0.18, 0.052, 0.15, 0.80

.;B;B;.;.;.;B;.;B;.;B;.;.;P

Vest4

0.44

MutPred

0.29

Loss of MoRF binding (P = 0.144);Loss of MoRF binding (P = 0.144);Loss of MoRF binding (P = 0.144);Loss of MoRF binding (P = 0.144);Loss of MoRF binding (P = 0.144);Loss of MoRF binding (P = 0.144);.;.;.;.;.;.;.;.;

MVP

0.043

MPC

1.5

ClinPred

0.85

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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