Genetic Variant NM_001048.4:c.91C>T (chr3-187670201-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001048.4(SST):c.91C>T(p.Leu31Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,386 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SST
NM_001048.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.78

Publications

0 publications found

Variant links:

Genes affected

SST (HGNC:11329): (somatostatin) The hormone somatostatin has active 14 aa and 28 aa forms that are produced by alternate cleavage of the single preproprotein encoded by this gene. Somatostatin is expressed throughout the body and inhibits the release of numerous secondary hormones by binding to high-affinity G-protein-coupled somatostatin receptors. This hormone is an important regulator of the endocrine system through its interactions with pituitary growth hormone, thyroid stimulating hormone, and most hormones of the gastrointestinal tract. Somatostatin also affects rates of neurotransmission in the central nervous system and proliferation of both normal and tumorigenic cells. [provided by RefSeq, Jul 2008]

SST links:

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ACMG classification

Classification was made for transcript

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=0.3483535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048.4. 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
	SST	NM_001048.4	MANE Select	c.91C>T	p.Leu31Phe	missense	Exon 1 of 2	NP_001039.1	P61278

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SST	ENST00000287641.4	TSL:1 MANE Select	c.91C>T	p.Leu31Phe	missense	Exon 1 of 2	ENSP00000287641.3	P61278

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33100

American (AMR)

AF:

0.00

AC:

AN:

41984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25764

East Asian (EAS)

AF:

0.00

AC:

AN:

38806

South Asian (SAS)

AF:

0.00

AC:

AN:

82946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103252

Other (OTH)

AF:

0.00

AC:

AN:

59678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.79

M_CAP

Benign

0.017

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

PhyloP100

7.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.2

REVEL

Benign

0.094

Sift

Benign

0.35

Sift4G

Benign

0.47

Polyphen

0.96

Vest4

0.45

MutPred

0.29

Loss of stability (P = 0.0853)

MVP

0.39

MPC

0.57

ClinPred

0.93

GERP RS

5.5

PromoterAI

0.025

Neutral

(source)

Varity_R

0.26

gMVP

0.30

Mutation Taster

=37/63

disease causing

(source)

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

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