7-116953668-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001369598.1(ST7):c.128A>C(p.Lys43Thr) 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. 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)
• Consequence: ST7 NM_001369598.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.818

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 Uncertain_significance. Variant got 2 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=0.28972125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST7	NM_001369598.1	c.128A>C	p.Lys43Thr	missense_variant	1/16	ENST00000323984.8
ST7-AS1	NR_002330.1	n.667T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST7	ENST00000323984.8	c.128A>C	p.Lys43Thr	missense_variant	1/16	5	NM_001369598.1
ST7-AS1	ENST00000456775.1	n.667T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jan 30, 2024

The c.128A>C (p.K43T) 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 128, causing the lysine (K) at amino acid position 43 to be replaced by a threonine (T). 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	0.75
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T;.;.;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	N;N;N;N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;D
Polyphen		0.51, 0.77	.;P;P;.;.;.
Vest4		0.39
MutPred		0.76		Loss of ubiquitination at K43 (P = 0.0218);Loss of ubiquitination at K43 (P = 0.0218);Loss of ubiquitination at K43 (P = 0.0218);Loss of ubiquitination at K43 (P = 0.0218);Loss of ubiquitination at K43 (P = 0.0218);Loss of ubiquitination at K43 (P = 0.0218);
MVP		0.043
MPC		0.18
ClinPred		0.40	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.87

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.

Other links and lift over

hg19: chr7-116593722;