Genetic Variant NM_000451.4:c.*16_*26dupCCCGCGCGCCC (chrX-644647-A-AGCCCCCCGCGC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000451.4(SHOX):c.*16_*26dupCCCGCGCGCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,452,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., 44 hem., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. 45 hem. )

Consequence

SHOX
NM_000451.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.631

Variant links:

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]

SHOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-644647-A-AGCCCCCCGCGC is Benign according to our data. Variant chrX-644647-A-AGCCCCCCGCGC is described in ClinVar as [Likely_benign]. Clinvar id is 256191.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000591 (90/152174) while in subpopulation AFR AF= 0.00207 (86/41516). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 44 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_000451.4 link	c.16_26dupCCCGCGCGCCC		3_prime_UTR_variant	Exon 5 of 5	ENST00000686671.1	NP_000442.1	O15266-1A0A024R385
SHOX	NM_006883.2 link	c.633+3565_633+3575dupCCCGCGCGCCC		intron_variant	Intron 5 of 5		NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SHOX	ENST00000686671.1 link	c.16_26dupCCCGCGCGCCC	3_prime_UTR_variant	Exon 5 of 5		NM_000451.4	ENSP00000508521.1	O15266-1
SHOX	ENST00000381575.6 link	c.633+3565_633+3575dupCCCGCGCGCCC	intron_variant	Intron 4 of 4	1		ENSP00000370987.1	O15266-2
SHOX	ENST00000381578.6 link	c.16_26dupCCCGCGCGCCC	3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000370990.1	O15266-1
SHOX	ENST00000334060.8 link	c.633+3565_633+3575dupCCCGCGCGCCC	intron_variant	Intron 5 of 5	5		ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74278

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000707

AC:

AN:

1300776

Hom.:

Cov.:

AF XY:

0.0000704

AC XY:

AN XY:

639442

show subpopulations

Gnomad4 AFR exome

AF:

0.00166

Gnomad4 AMR exome

AF:

0.0000911

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000393

Gnomad4 OTH exome

AF:

0.000111

GnomAD4 genome

AF:

0.000591

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000669

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

NM_000451.4:c.16_26dupCCCGCGCGCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over