3-158105069-A-G

Variant names:

• chr3-158105069-A-G
• rs1713794657
• ENST00000389589.8:c.407T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163678.2(SHOX2):​c.346+610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHOX2 NM_001163678.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 0 publications found

Genes affected

SHOX2 (HGNC:10854): (SHOX homeobox 2) This gene is a member of the homeobox family of genes that encode proteins containing a 60-amino acid residue motif that represents a DNA binding domain. Homeobox genes have been characterized extensively as transcriptional regulators involved in pattern formation in both invertebrate and vertebrate species. Several human genetic disorders are caused by aberrations in human homeobox genes. This locus represents a pseudoautosomal homeobox gene that is thought to be responsible for idiopathic short stature, and it is implicated in the short stature phenotype of Turner syndrome patients. This gene is considered to be a candidate gene for Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

SHOX2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061237723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX2	NM_001163678.2	c.346+610T>C		intron_variant	Intron 1 of 4	ENST00000483851.7	NP_001157150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX2	ENST00000483851.7	c.346+610T>C		intron_variant	Intron 1 of 4	2	NM_001163678.2	ENSP00000419362.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1010768 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 504458

African (AFR) AF: 0.00 AC: 0 AN: 22968

American (AMR) AF: 0.00 AC: 0 AN: 30342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17846

East Asian (EAS) AF: 0.00 AC: 0 AN: 18186

South Asian (SAS) AF: 0.00 AC: 0 AN: 72874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3036

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 771538

Other (OTH) AF: 0.00 AC: 0 AN: 39810

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.71
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.096
PrimateAI	Benign	0.42	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.26		Gain of glycosylation at S141 (P = 0.0287);
MVP		0.22
MPC		0.98
ClinPred		0.035	T
GERP RS		-0.094
gMVP		0.44
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs1713794657; hg19: chr3-157822858;