NM_021920.4:c.10C>T

Variant names:

• chr11-627134-G-A
• rs1427178586
• NM_021920.4:c.10C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021920.4(SCT):​c.10C>T​(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,080,592 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R4Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: SCT NM_021920.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.235
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2184298).

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.10C>T	p.Arg4Trp	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.10C>T	p.Arg4Trp	missense	Exon 1 of 4	ENSP00000176195.3	P09683

Frequencies

GnomAD3 genomes AF: 0.0000400 AC: 6 AN: 149928 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000596

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000322 AC: 3 AN: 930664 Hom.: 0 Cov.: 18 AF XY: 0.00000228 AC XY: 1 AN XY: 438310

African (AFR) AF: 0.00 AC: 0 AN: 18310

American (AMR) AF: 0.00 AC: 0 AN: 4656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8932

East Asian (EAS) AF: 0.00 AC: 0 AN: 13024

South Asian (SAS) AF: 0.00 AC: 0 AN: 17924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2230

European-Non Finnish (NFE) AF: 0.00000367 AC: 3 AN: 818122

Other (OTH) AF: 0.00 AC: 0 AN: 34180

GnomAD4 genome AF: 0.0000400 AC: 6 AN: 149928 Hom.: 0 Cov.: 32 AF XY: 0.0000684 AC XY: 5 AN XY: 73110

African (AFR) AF: 0.0000485 AC: 2 AN: 41206

American (AMR) AF: 0.00 AC: 0 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000596 AC: 4 AN: 67134

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.23
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.029
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.22
MutPred		0.35		Gain of catalytic residue at R4 (P = 0.0042)
MVP		0.56
MPC		0.26
ClinPred		0.32	T
GERP RS		1.1
PromoterAI		-0.0036	Neutral
Varity_R		0.10
gMVP		0.24
Mutation Taster		=92/8	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: rs1427178586; hg19: chr11-627134;