7-117138504-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001369598.1(ST7):c.935C>T(p.Thr312Ile) 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. 13/21 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: ST7 NM_001369598.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ST7
• BP4: Computational evidence support a benign effect (MetaRNN=0.23179245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST7	NM_001369598.1	c.935C>T	p.Thr312Ile	missense_variant	9/16	ENST00000323984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST7	ENST00000323984.8	c.935C>T	p.Thr312Ile	missense_variant	9/16	5	NM_001369598.1
ST7-AS2	ENST00000432541.5	n.250+5663G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 22, 2023

The c.935C>T (p.T312I) alteration is located in exon 9 (coding exon 9) of the ST7 gene. This alteration results from a C to T substitution at nucleotide position 935, causing the threonine (T) at amino acid position 312 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
Cadd	Benign	22
Dann	Benign	0.91
DEOGEN2	Benign	0.0035	T;T;.;.;T;.;T;T;.;T;T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;T;T;T;D;T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.78	N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.56	T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T;T;T;T;.;T;T;T
Polyphen		0.0010, 0.021, 0.0040, 1.0	.;B;B;.;.;.;B;.;B;B;.;D
Vest4		0.41
MutPred		0.31		.;Loss of phosphorylation at T312 (P = 0.0157);.;Loss of phosphorylation at T312 (P = 0.0157);Loss of phosphorylation at T312 (P = 0.0157);.;.;.;.;.;.;.;
MVP		0.082
MPC		2.1
ClinPred		0.70	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.66

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

Other links and lift over

dbSNP: rs980558084; hg19: chr7-116778558;