chr1-112582427-A-G

Variant names:

• chr1-112582427-A-G
• rs562339819
• NM_017744.5:c.902T>C

Variant summary

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

The NM_017744.5(ST7L):​c.902T>C​(p.Met301Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,609,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M301V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: ST7L NM_017744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST7L	NM_017744.5	c.902T>C	p.Met301Thr	missense_variant	Exon 8 of 15	ENST00000358039.9	NP_060214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST7L	ENST00000358039.9	c.902T>C	p.Met301Thr	missense_variant	Exon 8 of 15	1	NM_017744.5	ENSP00000350734.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000999 AC: 25 AN: 250126 AF XY: 0.000177

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000432 AC: 63 AN: 1456942 Hom.: 0 Cov.: 29 AF XY: 0.0000690 AC XY: 50 AN XY: 725084

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.000698 AC: 60 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109104

Other (OTH) AF: 0.0000498 AC: 3 AN: 60246

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74434

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.000148 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.902T>C (p.M301T) alteration is located in exon 8 (coding exon 8) of the ST7L gene. This alteration results from a T to C substitution at nucleotide position 902, causing the methionine (M) at amino acid position 301 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	0.83
BayesDel_addAF	Benign	-0.0087	T
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	.;T;.;.;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.9	M;M;.;.;M;.
PhyloP100		8.9
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-4.9	D;D;D;D;D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D
Polyphen		0.98	D;D;.;P;D;D
Vest4		0.89
MutPred		0.73		Gain of phosphorylation at M301 (P = 0.0534);Gain of phosphorylation at M301 (P = 0.0534);.;.;Gain of phosphorylation at M301 (P = 0.0534);.;
MVP		0.58
MPC		0.48
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.74
Mutation Taster		=0/100	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

dbSNP: rs562339819; hg19: chr1-113125049;