chr1-26022696-C-T

Variant names:

• chr1-26022696-C-T
• rs141728988
• NM_004455.3:c.50C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004455.3(EXTL1):​c.50C>T​(p.Ser17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,612,788 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (2 hom.)
• Consequence: EXTL1 NM_004455.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.912
• Publications: 4 publications found

Genes affected

EXTL1 (HGNC:3515): (exostosin like glycosyltransferase 1) This gene is a member of the multiple exostoses (EXT) family of glycosyltransferases, which function in the chain polymerization of heparan sulfate and heparin. The encoded protein harbors alpha 1,4- N-acetylglucosaminyltransferase activity, and is involved in chain elongation of heparan sulfate and possibly heparin. [provided by RefSeq, Jul 2008]

ENSG00000310101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04083234).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004455.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL1	NM_004455.3	MANE Select	c.50C>T	p.Ser17Phe	missense	Exon 1 of 11	NP_004446.2	Q92935

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL1	ENST00000374280.4	TSL:1 MANE Select	c.50C>T	p.Ser17Phe	missense	Exon 1 of 11	ENSP00000363398.3	Q92935
	EXTL1	ENST00000882621.1		c.50C>T	p.Ser17Phe	missense	Exon 1 of 11	ENSP00000552680.1
	EXTL1	ENST00000882616.1		c.50C>T	p.Ser17Phe	missense	Exon 1 of 10	ENSP00000552675.1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000523 AC: 131 AN: 250290 AF XY: 0.000481

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000932 AC: 1362 AN: 1460662 Hom.: 2 Cov.: 33 AF XY: 0.000878 AC XY: 638 AN XY: 726506

African (AFR) AF: 0.000179 AC: 6 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86052

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00119 AC: 1319 AN: 1111396

Other (OTH) AF: 0.000365 AC: 22 AN: 60356

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 30 AN XY: 74306

African (AFR) AF: 0.000145 AC: 6 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000816 Hom.: 0

Bravo AF: 0.000382

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000642 AC: 78

EpiCase AF: 0.000763

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.041	T
MetaSVM	Uncertain	-0.089	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.91
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.23
Sift	Benign	0.48	T
Sift4G	Benign	0.33	T
Polyphen		0.030	B
Vest4		0.24
MVP		0.68
MPC		0.34
ClinPred		0.012	T
GERP RS		3.4
Varity_R		0.072
gMVP		0.67
Mutation Taster		=79/21	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: rs141728988; hg19: chr1-26349187;