rs1556457962

Variant names:

• chrX-631133-A-G
• NM_000451.4:c.236A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-631133-A-G
• chrX-631133-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000451.4(SHOX):​c.236A>G​(p.Lys79Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,212 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom. 1 hem.)
• Consequence: SHOX NM_000451.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15

Genes affected

SHOX (HGNC:10853): (SHOX homeobox) This gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. Defects in this gene are associated with idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients. This gene is highly conserved across species from mammals to fish to flies. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19638368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_000451.4	c.236A>G	p.Lys79Arg	missense_variant	Exon 1 of 5	ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2	c.236A>G	p.Lys79Arg	missense_variant	Exon 2 of 6		NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000686671.1	c.236A>G	p.Lys79Arg	missense_variant	Exon 1 of 5		NM_000451.4	ENSP00000508521.1
SHOX	ENST00000381575.6	c.236A>G	p.Lys79Arg	missense_variant	Exon 1 of 5	1		ENSP00000370987.1
SHOX	ENST00000381578.6	c.236A>G	p.Lys79Arg	missense_variant	Exon 2 of 6	5		ENSP00000370990.1
SHOX	ENST00000334060.8	c.236A>G	p.Lys79Arg	missense_variant	Exon 2 of 6	5		ENSP00000335505.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461212 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.030	T;.;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.10
MutPred		0.45		Loss of ubiquitination at K79 (P = 0.0118);Loss of ubiquitination at K79 (P = 0.0118);Loss of ubiquitination at K79 (P = 0.0118);
MVP		0.75
MPC		0.47
ClinPred		0.53	D
GERP RS		2.3
Varity_R		0.093

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-591868;