NM_017744.5:c.1466C>T

Variant names:

• chr1-112550624-G-A
• rs142542242
• NM_017744.5:c.1466C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017744.5(ST7L):​c.1466C>T​(p.Thr489Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,612,938 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: ST7L NM_017744.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.95
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025365531).
• BP6: Variant 1-112550624-G-A is Benign according to our data. Variant chr1-112550624-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2353806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST7L	NM_017744.5	c.1466C>T	p.Thr489Met	missense_variant	Exon 13 of 15	ENST00000358039.9	NP_060214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST7L	ENST00000358039.9	c.1466C>T	p.Thr489Met	missense_variant	Exon 13 of 15	1	NM_017744.5	ENSP00000350734.4

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000302 AC: 76 AN: 251244 AF XY: 0.000309

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000151 AC: 220 AN: 1460770 Hom.: 2 Cov.: 29 AF XY: 0.000158 AC XY: 115 AN XY: 726728

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.000179 AC: 8 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 69 AN: 26112

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39602

South Asian (SAS) AF: 0.000743 AC: 64 AN: 86138

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53376

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111290

Other (OTH) AF: 0.000315 AC: 19 AN: 60336

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41520

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000202 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000272 AC: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3474

EpiCase AF: 0.000274

EpiControl AF: 0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 15, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T;.;.;.;.
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.0098
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;T;T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.025	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.;M;.
PhyloP100		3.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.092	T;T;T;T;T
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		0.94	P;.;P;P;D
Vest4		0.28
MVP		0.42
MPC		0.11
ClinPred		0.071	T
GERP RS		2.8
Varity_R		0.034
gMVP		0.71
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs142542242; hg19: chr1-113093246;