Genetic Variant SCTR:p.Gly257Val (chr2-119461867-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002980.3(SCTR):c.770G>T(p.Gly257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G257E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SCTR
NM_002980.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09

Publications

0 publications found

Variant links:

Genes affected

SCTR (HGNC:10608): (secretin receptor) The protein encoded by this gene is a G protein-coupled receptor and belongs to the glucagon-VIP-secretin receptor family. It binds secretin which is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. Secretin and its receptor are suggested to be involved in pancreatic cancer and autism. [provided by RefSeq, Jul 2008]

SCTR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002980.3. 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
	SCTR	NM_002980.3	MANE Select	c.770G>T	p.Gly257Val	missense	Exon 7 of 13	NP_002971.2	P47872

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCTR	ENST00000019103.8	TSL:1 MANE Select	c.770G>T	p.Gly257Val	missense	Exon 7 of 13	ENSP00000019103.6	P47872
SCTR	ENST00000903274.1		c.965G>T	p.Gly322Val	missense	Exon 9 of 15	ENSP00000573333.1
SCTR	ENST00000903275.1		c.770G>T	p.Gly257Val	missense	Exon 7 of 13	ENSP00000573334.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250674

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000479

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111738

Other (OTH)

AF:

0.00

AC:

AN:

60380

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.13

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.73

M_CAP

Benign

0.0035

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

3.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

REVEL

Benign

0.065

Sift

Benign

0.60

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.38

MutPred

0.68

Loss of ubiquitination at K253 (P = 0.0949)

MVP

0.47

MPC

0.12

ClinPred

0.075

GERP RS

2.2

Varity_R

0.16

gMVP

0.38

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.98

Position offset: 2

DS_DL_spliceai

0.90

Position offset: -20

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