chr1-112583986-T-C

Variant names:

• chr1-112583986-T-C
• NM_017744.5:c.842A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017744.5(ST7L):​c.842A>G​(p.His281Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST7L NM_017744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37614077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST7L	NM_017744.5	c.842A>G	p.His281Arg	missense_variant	Exon 7 of 15	ENST00000358039.9	NP_060214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST7L	ENST00000358039.9	c.842A>G	p.His281Arg	missense_variant	Exon 7 of 15	1	NM_017744.5	ENSP00000350734.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.842A>G (p.H281R) alteration is located in exon 7 (coding exon 7) of the ST7L gene. This alteration results from a A to G substitution at nucleotide position 842, causing the histidine (H) at amino acid position 281 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	Benign	0.096
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.015	.;T;.;.;.;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.38	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L;L;.;.;L;.;.
PhyloP100		7.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.7	D;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.28	T;T;T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T;.
Polyphen		0.0020	B;B;.;B;B;B;.
Vest4		0.54
MutPred		0.36		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;.;Gain of helix (P = 0.0425);.;.;
MVP		0.53
MPC		0.29
ClinPred		0.94	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.58
Mutation Taster		=25/75	disease causing

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

Other links and lift over

hg19: chr1-113126608; COSMIC: COSV58311248;