Variant chr7-117119702-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_001369598.1(ST7):c.376A>T(p.Asn126Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ST7
NM_001369598.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.19

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:

ENSG00000288635 (HGNC:):

ENSG00000288635 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.33191922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST7	NM_001369598.1 linkuse as main transcript	c.376A>T	p.Asn126Tyr	missense_variant	3/16	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.376A>T	p.Asn126Tyr	missense_variant	3/16	5	NM_001369598.1	ENSP00000325673.3		H7BXS2
ENSG00000288635	ENST00000421345.5 linkuse as main transcript	c.220A>T	p.Asn74Tyr	missense_variant	3/3	4		ENSP00000416858.1		C9JCI7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460564

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726468

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 07, 2024

The c.376A>T (p.N126Y) alteration is located in exon 3 (coding exon 3) of the ST7 gene. This alteration results from a A to T substitution at nucleotide position 376, causing the asparagine (N) at amino acid position 126 to be replaced by a tyrosine (Y). 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

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

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

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.022

MetaRNN

Benign

0.33

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

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

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.1

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

REVEL

Benign

0.19

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D;D;D;.;.;D;D;D;D;D;D

Polyphen

0.92, 0.55, 0.56, 0.65, 0.59, 0.97

.;P;P;.;.;.;.;P;.;.;P;.;.;P;.;.;D

Vest4

0.46

MutPred

0.36

Gain of phosphorylation at N126 (P = 0.0452);Gain of phosphorylation at N126 (P = 0.0452);Gain of phosphorylation at N126 (P = 0.0452);Gain of phosphorylation at N126 (P = 0.0452);Gain of phosphorylation at N126 (P = 0.0452);Gain of phosphorylation at N126 (P = 0.0452);.;.;.;.;.;.;.;.;.;.;.;

MVP

0.043

MPC

2.1

ClinPred

0.91

GERP RS

6.1

Varity_R

0.35

gMVP

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over