chr11-627133-C-T

Variant names:

• chr11-627133-C-T
• rs903918685
• NM_021920.4:c.11G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021920.4(SCT):​c.11G>A​(p.Arg4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000567 in 289,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: SCT NM_021920.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.48
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053502977).

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.11G>A	p.Arg4Gln	missense	Exon 1 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.11G>A	p.Arg4Gln	missense	Exon 1 of 4	ENSP00000176195.3	P09683

Frequencies

GnomAD3 genomes AF: 0.0000656 AC: 9 AN: 137184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000251

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000112

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00102 AC: 155 AN: 152298 Hom.: 0 Cov.: 4 AF XY: 0.00102 AC XY: 76 AN XY: 74414

African (AFR) AF: 0.000311 AC: 1 AN: 3212

American (AMR) AF: 0.00 AC: 0 AN: 1862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2476

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000386 AC: 1 AN: 2594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 508

European-Non Finnish (NFE) AF: 0.00117 AC: 146 AN: 124300

Other (OTH) AF: 0.00101 AC: 7 AN: 6940

GnomAD4 genome AF: 0.0000656 AC: 9 AN: 137184 Hom.: 0 Cov.: 31 AF XY: 0.0000749 AC XY: 5 AN XY: 66712

African (AFR) AF: 0.0000264 AC: 1 AN: 37850

American (AMR) AF: 0.00 AC: 0 AN: 13920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3210

East Asian (EAS) AF: 0.00 AC: 0 AN: 4388

South Asian (SAS) AF: 0.000251 AC: 1 AN: 3992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.000112 AC: 7 AN: 62666

Other (OTH) AF: 0.00 AC: 0 AN: 1920

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

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	Benign	0.33
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0030	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PhyloP100		-2.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.41	T
Polyphen		0.028	B
Vest4		0.037
MutPred		0.22		Loss of methylation at R4 (P = 0.041)
MVP		0.14
MPC		0.29
ClinPred		0.051	T
GERP RS		-4.2
PromoterAI		-0.032	Neutral
Varity_R		0.087
gMVP		0.18
Mutation Taster		=96/4	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: rs903918685; hg19: chr11-627133;