11-626736-A-G

Variant names:

• chr11-626736-A-G
• rs1195011573
• NM_021920.4:c.227T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021920.4(SCT):​c.227T>C​(p.Leu76Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L76F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCT NM_021920.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 0 publications found

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]

ACMG classification

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.227T>C	p.Leu76Pro	missense	Exon 3 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.227T>C	p.Leu76Pro	missense	Exon 3 of 4	ENSP00000176195.3	P09683

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000372 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.38	N
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.43
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.95	P
Vest4		0.44
MutPred		0.53		Gain of disorder (P = 0.0076)
MVP		0.70
MPC		1.1
ClinPred		0.70	D
GERP RS		2.8
PromoterAI		0.00060	Neutral
Varity_R		0.48
gMVP		0.26
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1195011573; hg19: chr11-626736;