rs780543135

Variant names:

• chr1-112542090-G-A
• rs780543135
• NM_017744.5:c.1490C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-112542090-G-A
• chr1-112542090-G-C

Variant summary

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

The NM_017744.5(ST7L):​c.1490C>T​(p.Thr497Ile) 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. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T497S) has been classified 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: 0.09286
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03
• 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=0.3403152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST7L	NM_017744.5	c.1490C>T	p.Thr497Ile	missense_variant, splice_region_variant	Exon 14 of 15	ENST00000358039.9	NP_060214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST7L	ENST00000358039.9	c.1490C>T	p.Thr497Ile	missense_variant, splice_region_variant	Exon 14 of 15	1	NM_017744.5	ENSP00000350734.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452438 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722342

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32978

American (AMR) AF: 0.00 AC: 0 AN: 43052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25840

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.00 AC: 0 AN: 84232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1108004

Other (OTH) AF: 0.00 AC: 0 AN: 59962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0073	.;T;.;.;.;.
Eigen	Benign	0.066
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.;.;L;.
PhyloP100		5.0
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.8	D;N;N;N;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;T;D;D;D
Polyphen		1.0	D;B;.;B;B;B
Vest4		0.65
MutPred		0.40		.;Loss of glycosylation at T497 (P = 0.0048);.;.;Loss of glycosylation at T497 (P = 0.0048);.;
MVP		0.49
MPC		0.21
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.72
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.093
dbscSNV1_RF	Benign	0.41
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.32		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs780543135; hg19: chr1-113084712;