Genetic Variant SCT:p.Arg26Gln (chr11-626984-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021920.4(SCT):c.77G>A(p.Arg26Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,277,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SCT
NM_021920.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.77

Publications

1 publications found

Variant links:

Genes affected

SCT (HGNC:10607): (secretin) This gene encodes a member of the glucagon family of peptides. The encoded preproprotein is secreted by endocrine S cells in the proximal small intestinal mucosa as a prohormone, then proteolytically processed to generate the mature peptide hormone. The release of this active peptide hormone is stimulated by either fatty acids or acidic pH in the duodenum. This hormone stimulates the secretion of bile and bicarbonate in the duodenum, pancreatic and biliary ducts. [provided by RefSeq, Feb 2016]

SCT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02066791).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021920.4. 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
	SCT	NM_021920.4	MANE Select	c.77G>A	p.Arg26Gln	missense	Exon 2 of 4	NP_068739.1	P09683

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCT	ENST00000176195.4	TSL:1 MANE Select	c.77G>A	p.Arg26Gln	missense	Exon 2 of 4	ENSP00000176195.3	P09683

Frequencies

GnomAD3 genomes

AF:

0.0000635

AC:

AN:

141718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000261

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000155

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000658

AC:

AN:

121536

AF XY:

0.0000748

show subpopulations

Gnomad AFR exome

AF:

0.000206

Gnomad AMR exome

AF:

0.000126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000223

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1136004

Hom.:

Cov.:

AF XY:

0.0000233

AC XY:

AN XY:

557124

show subpopulations

African (AFR)

AF:

0.000376

AC:

AN:

23916

American (AMR)

AF:

0.000141

AC:

AN:

28294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16222

East Asian (EAS)

AF:

0.00

AC:

AN:

13384

South Asian (SAS)

AF:

0.000119

AC:

AN:

75886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2812

European-Non Finnish (NFE)

AF:

0.00000652

AC:

AN:

920234

Other (OTH)

AF:

0.0000478

AC:

AN:

41852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000635

AC:

AN:

141718

Hom.:

Cov.:

AF XY:

0.0000436

AC XY:

AN XY:

68790

show subpopulations

African (AFR)

AF:

0.000176

AC:

AN:

39722

American (AMR)

AF:

0.00

AC:

AN:

14398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3352

East Asian (EAS)

AF:

0.00

AC:

AN:

4056

South Asian (SAS)

AF:

0.000261

AC:

AN:

3828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

64620

Other (OTH)

AF:

0.00

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000602

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0031

M_CAP

Benign

0.031

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-1.8

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.38

REVEL

Benign

0.029

Sift

Benign

0.25

Sift4G

Benign

0.36

Polyphen

0.0060

Vest4

0.049

MutPred

0.10

Loss of methylation at R26 (P = 0.0273)

MVP

0.11

MPC

0.29

ClinPred

0.016

GERP RS

-5.3

PromoterAI

0.024

Neutral

(source)

Varity_R

0.031

gMVP

0.11

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over