chr1-112541974-T-C

Variant summary

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

The NM_017744.5(ST7L):​c.1606A>G​(p.Ile536Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ST7L
NM_017744.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Publications

2 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]

Genome browser will be placed here

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=0.08999097).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST7LNM_017744.5 linkc.1606A>G p.Ile536Val missense_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
ST7LENST00000358039.9 linkc.1606A>G p.Ile536Val missense_variant Exon 14 of 15 1 NM_017744.5 ENSP00000350734.4 Q8TDW4-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461530
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727052
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44662
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39644
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111890
Other (OTH)
AF:
0.00
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41452
American (AMR)
AF:
0.00
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.000192
AC:
1
AN:
5204
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1606A>G (p.I536V) alteration is located in exon 14 (coding exon 14) of the ST7L gene. This alteration results from a A to G substitution at nucleotide position 1606, causing the isoleucine (I) at amino acid position 536 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
0.11
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.0030
.;T;.;.;.;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.082
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
T;T;T;T;T;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.090
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;N;.;.;N;.
PhyloP100
5.9
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.28
N;N;N;N;N;N
REVEL
Benign
0.051
Sift
Benign
0.50
T;T;T;T;T;T
Sift4G
Benign
0.70
T;T;T;T;T;T
Polyphen
0.0010
B;B;.;B;B;B
Vest4
0.16
MutPred
0.33
.;Loss of helix (P = 0.2271);.;.;Loss of helix (P = 0.2271);.;
MVP
0.41
MPC
0.069
ClinPred
0.39
T
GERP RS
3.6
Varity_R
0.026
gMVP
0.16
Mutation Taster
=87/13
polymorphism

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

Other links and lift over

dbSNP: rs1277862906; hg19: chr1-113084596; API