Genetic Variant NM_017744.5:c.1490C>G (chr1-112542090-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017744.5(ST7L):c.1490C>G(p.Thr497Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000138 in 1,452,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ST7L
NM_017744.5 missense, splice_region

Scores

Splicing: ADA: 0.0002379

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Publications

0 publications found

Variant links:

Genes affected

ST7L (HGNC:18441): (suppression of tumorigenicity 7 like) This gene was identified by its similarity to the ST7 tumor suppressor gene found in the chromosome 7q31 region. This gene is clustered in a tail-to-tail manner with the WNT2B gene in a chromosomal region known to be deleted and rearranged in a variety of cancers. Several transcript variants encoding many different isoforms have been described, but some have not been fully characterized. [provided by RefSeq, Feb 2011]

ST7L links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13568267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST7L	NM_017744.5 link	c.1490C>G	p.Thr497Ser	missense_variant, splice_region_variant	Exon 14 of 15	ENST00000358039.9	NP_060214.2	Q8TDW4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST7L	ENST00000358039.9 link	c.1490C>G	p.Thr497Ser	missense_variant, splice_region_variant	Exon 14 of 15	1	NM_017744.5	ENSP00000350734.4		Q8TDW4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243298

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452438

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32978

American (AMR)

AF:

0.00

AC:

AN:

43052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.00

AC:

AN:

39376

South Asian (SAS)

AF:

0.00

AC:

AN:

84232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1108004

Other (OTH)

AF:

0.00

AC:

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1490C>G (p.T497S) alteration is located in exon 14 (coding exon 14) of the ST7L gene. This alteration results from a C to G substitution at nucleotide position 1490, causing the threonine (T) at amino acid position 497 to be replaced by a serine (S). 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

0.064

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.00064

.;T;.;.;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

T;T;T;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.36

.;N;.;.;N;.

PhyloP100

5.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.4

N;N;N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.031

D;T;T;T;T;T

Sift4G

Uncertain

0.059

T;T;T;T;T;T

Polyphen

0.63

P;B;.;B;B;B

Vest4

0.36

MutPred

0.61

Loss of helix (P = 0.0558);Loss of glycosylation at T497 (P = 0.0118);.;.;Loss of glycosylation at T497 (P = 0.0118);.;

MVP

0.26

MPC

0.073

ClinPred

0.19

GERP RS

5.2

Varity_R

0.11

gMVP

0.40

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.20

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

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NM_017744.5:c.1490C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over