7-116953551-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Moderate BS2

The NM_001369598.1(ST7):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,412,186 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: 𝑓 0.000027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: ST7 NM_001369598.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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 -5 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ST7
• BP4: Computational evidence support a benign effect (MetaRNN=0.11976385).
• BS2: High AC in GnomAdExome at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST7	NM_001369598.1	c.11C>T	p.Ala4Val	missense_variant	1/16	ENST00000323984.8
ST7-AS1	NR_002330.1	n.784G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST7	ENST00000323984.8	c.11C>T	p.Ala4Val	missense_variant	1/16	5	NM_001369598.1
ST7-AS1	ENST00000456775.1	n.784G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 4 AN: 148924 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000200

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000404 AC: 8 AN: 198078 Hom.: 0 AF XY: 0.0000184 AC XY: 2 AN XY: 108924

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000155

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: 0.0000219

Gnomad OTH exome AF: 0.000460

GnomAD4 exome AF: 0.0000309 AC: 39 AN: 1263262 Hom.: 0 Cov.: 31 AF XY: 0.0000335 AC XY: 21 AN XY: 627458

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.000239

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: 0.0000252

Gnomad4 OTH exome AF: 0.0000824

GnomAD4 genome AF: 0.0000269 AC: 4 AN: 148924 Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 2 AN XY: 72636

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000200

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000247 AC: 3

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

Apr 07, 2022

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the ST7 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	17
Dann	Benign	0.96
DEOGEN2	Benign	0.010	T;T;.;.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.50	N
LIST_S2	Uncertain	0.88	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
MutationTaster	Benign	0.65	N;N;N;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.46	N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.057	T;D;T;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.96, 0.98	.;D;D;.;.;.
Vest4		0.22
MutPred		0.13		Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);
MVP		0.043
MPC		0.13
ClinPred		0.28	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.81

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: rs770090404; hg19: chr7-116593605;