Genetic Variant SCT:p.Asp93Asn (chr11-626520-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021920.4(SCT):c.277G>A(p.Asp93Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SCT
NM_021920.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.53

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06337577).

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.277G>A	p.Asp93Asn	missense	Exon 4 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.277G>A	p.Asp93Asn	missense	Exon 4 of 4	ENSP00000176195.3	P09683

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

165216

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1406292

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31974

American (AMR)

AF:

0.00

AC:

AN:

36578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25244

East Asian (EAS)

AF:

0.00

AC:

AN:

36476

South Asian (SAS)

AF:

0.00

AC:

AN:

79658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1082982

Other (OTH)

AF:

0.00

AC:

AN:

58278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

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

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.3

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.015

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

-1.5

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

REVEL

Benign

0.027

Sift

Benign

0.071

Sift4G

Pathogenic

0.0

Polyphen

0.017

Vest4

0.10

MutPred

0.29

Gain of glycosylation at T95 (P = 0.1072)

MVP

0.24

MPC

0.25

ClinPred

0.070

GERP RS

1.1

PromoterAI

0.021

Neutral

(source)

Varity_R

0.041

gMVP

0.093

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over