Genetic Variant NM_021920.4:c.122G>C (chr11-626939-C-G) – 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_021920.4(SCT):c.122G>C(p.Arg41Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,510 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R41R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SCT
NM_021920.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.123

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:

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;

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.122G>C	p.Arg41Pro	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.122G>C	p.Arg41Pro	missense	Exon 2 of 4	ENSP00000176195.3	P09683

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000764

AC:

AN:

130872

AF XY:

0.00

show subpopulations

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:

0.0000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1383510

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31454

American (AMR)

AF:

0.00

AC:

AN:

35612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

35662

South Asian (SAS)

AF:

0.00

AC:

AN:

79116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4750

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1077826

Other (OTH)

AF:

0.00

AC:

AN:

57702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Pathogenic

0.81

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.44

Eigen

Benign

0.017

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.12

M_CAP

Uncertain

0.26

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PhyloP100

0.12

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.13

Sift

Uncertain

0.012

Sift4G

Uncertain

0.026

Polyphen

1.0

Vest4

0.21

MutPred

0.62

Loss of MoRF binding (P = 6e-04)

MVP

0.50

MPC

0.90

ClinPred

0.92

GERP RS

1.8

PromoterAI

0.012

Neutral

(source)

Varity_R

0.89

gMVP

0.33

Mutation Taster

=92/8

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over