dbSNP rs71739430: EXT1:c.*140_*144delAAAAA (chr8-117799567-CTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000127.3(EXT1):c.*140_*144delAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 642,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

EXT1
NM_000127.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

0 publications found

Variant links:

Genes affected

EXT1 (HGNC:3512): (exostosin glycosyltransferase 1) This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of multiple exostoses. [provided by RefSeq, Jul 2008]

EXT1 Gene-Disease associations (from GenCC):

exostoses, multiple, type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
chondrosarcoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
hereditary multiple osteochondromas
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EXT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXT1	NM_000127.3 link	c.140_144delAAAAA		3_prime_UTR_variant	Exon 11 of 11	ENST00000378204.7	NP_000118.2	Q16394

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EXT1	ENST00000378204.7 link	c.140_144delAAAAA	3_prime_UTR_variant	Exon 11 of 11	1	NM_000127.3	ENSP00000367446.3	Q16394
EXT1	ENST00000684189.1 link	n.1848_1852delAAAAA	non_coding_transcript_exon_variant	Exon 11 of 11
EXT1	ENST00000437196.1 link	n.1272_1276delAAAAA	downstream_gene_variant		5		ENSP00000407299.1	F8WF54
EXT1	ENST00000684443.1 link	n.15_19delAAAAA	downstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000156

AC:

AN:

642864

Hom.:

AF XY:

0.00000300

AC XY:

AN XY:

333000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15314

American (AMR)

AF:

0.00

AC:

AN:

23936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15506

East Asian (EAS)

AF:

0.00

AC:

AN:

27802

South Asian (SAS)

AF:

0.00

AC:

AN:

49894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3050

European-Non Finnish (NFE)

AF:

0.00000226

AC:

AN:

441646

Other (OTH)

AF:

0.00

AC:

AN:

30988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over