7-116953685-A-C

Position:

• chr7-116953685-A-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2 PP2 BP4_Moderate BS2

The NM_001369598.1(ST7):​c.145A>C​(p.Ser49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,338,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000037 (0 hom.)
• Consequence: ST7 NM_001369598.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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:):

ACMG classification

Verdict is Likely_benign. Variant got -3 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=0.12016767).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST7	NM_001369598.1	c.145A>C	p.Ser49Arg	missense_variant	1/16	ENST00000323984.8	NP_001356527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST7	ENST00000323984.8	c.145A>C	p.Ser49Arg	missense_variant	1/16	5	NM_001369598.1	ENSP00000325673.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000373 AC: 5 AN: 1338876 Hom.: 0 Cov.: 31 AF XY: 0.00000450 AC XY: 3 AN XY: 666800

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: 0.00000482

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

Dec 28, 2023

The c.145A>C (p.S49R) 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 145, causing the serine (S) at amino acid position 49 to be replaced by an arginine (R). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T;.;.;T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;L;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.13	T;T;T;T;T;D
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.19, 0.048	.;B;B;.;.;.
Vest4		0.23
MutPred		0.23		Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);
MVP		0.043
MPC		2.3
ClinPred		0.24	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.75

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: rs1361699852; hg19: chr7-116593739;