7-116953586-A-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_001369598.1(ST7):c.46A>C(p.Ile16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,338,396 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: not found (cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ST7 NM_001369598.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39

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

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ST7
• BP4: Computational evidence support a benign effect (MetaRNN=0.083768874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST7	NM_001369598.1	c.46A>C	p.Ile16Leu	missense_variant	1/16	ENST00000323984.8
ST7-AS1	NR_002330.1	n.749T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST7	ENST00000323984.8	c.46A>C	p.Ile16Leu	missense_variant	1/16	5	NM_001369598.1
ST7-AS1	ENST00000456775.1	n.749T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000194 AC: 26 AN: 1338396 Hom.: 0 Cov.: 31 AF XY: 0.0000180 AC XY: 12 AN XY: 666892

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: 0.0000251

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

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

Mar 02, 2023

The c.46A>C (p.I16L) alteration is located in exon 1 (coding exon 1) of the ST7 gene. This alteration results from a A to C substitution at nucleotide position 46, causing the isoleucine (I) at amino acid position 16 to be replaced by a leucine (L). 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	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	16
Dann	Benign	0.94
DEOGEN2	Benign	0.0068	T;T;.;.;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.084	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.99	N;N;N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.060	N;N;N;N;N;N
REVEL	Benign	0.081
Sift	Benign	0.73	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0, 0.10	.;B;B;.;.;.
Vest4		0.35
MutPred		0.60		Gain of ubiquitination at K13 (P = 0.1008);Gain of ubiquitination at K13 (P = 0.1008);Gain of ubiquitination at K13 (P = 0.1008);Gain of ubiquitination at K13 (P = 0.1008);Gain of ubiquitination at K13 (P = 0.1008);Gain of ubiquitination at K13 (P = 0.1008);
MVP		0.043
MPC		0.13
ClinPred		0.18	T
GERP RS		2.4
Varity_R		0.071
gMVP		0.59

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: rs766059066; hg19: chr7-116593640;