rs199636057

Variant names:

• chr2-119461980-C-A
• rs199636057
• NM_002980.3:c.657G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-119461980-C-A
• chr2-119461980-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002980.3(SCTR):​c.657G>T​(p.Met219Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,606,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SCTR NM_002980.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32632512).

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.657G>T	p.Met219Ile	missense	Exon 7 of 13	NP_002971.2	P47872

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCTR	ENST00000019103.8	TSL:1 MANE Select	c.657G>T	p.Met219Ile	missense	Exon 7 of 13	ENSP00000019103.6	P47872
	SCTR	ENST00000903274.1		c.852G>T	p.Met284Ile	missense	Exon 9 of 15	ENSP00000573333.1
	SCTR	ENST00000903275.1		c.657G>T	p.Met219Ile	missense	Exon 7 of 13	ENSP00000573334.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000246 AC: 6 AN: 243938 AF XY: 0.0000379

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: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 31 AN: 1454408 Hom.: 0 Cov.: 31 AF XY: 0.0000235 AC XY: 17 AN XY: 723298

African (AFR) AF: 0.00 AC: 0 AN: 33150

American (AMR) AF: 0.00 AC: 0 AN: 43654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39290

South Asian (SAS) AF: 0.000106 AC: 9 AN: 84690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1108628

Other (OTH) AF: 0.0000333 AC: 2 AN: 60074

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.013
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.18
Sift	Benign	0.094	T
Sift4G	Benign	0.13	T
Polyphen		0.12	B
Vest4		0.50
MutPred		0.52		Loss of catalytic residue at M219 (P = 0.0057)
MVP		0.60
MPC		0.41
ClinPred		0.79	D
GERP RS		5.1
Varity_R		0.61
gMVP		0.39
Mutation Taster		=48/52	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs199636057; hg19: chr2-120219556;