Genetic Variant NM_001172560.3:c.76A>C (chr16-1078944-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2

The NM_001172560.3(SSTR5):c.76A>C(p.Asn26His) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,598,566 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SSTR5
NM_001172560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

SSTR5 (HGNC:11334): (somatostatin receptor 5) Somatostatin and its related peptide cortistatin exert multiple biological actions on normal and tumoral tissue targets by interacting with somatostatin receptors (SSTRs). The protein encoded by this gene is one of the SSTRs, which is a multi-pass membrane protein and belongs to the G-protein coupled receptor 1 family. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase, and different regions of this receptor molecule are required for the activation of different signaling pathways. A mutation in this gene results in somatostatin analog resistance. Alternatively spliced transcript variants have been identified in this gene.[provided by RefSeq, Feb 2010]

SSTR5 links:

SSTR5-AS1 (HGNC:26502): (SSTR5 antisense RNA 1)

SSTR5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity SSR5_HUMAN

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3 link	c.76A>C	p.Asn26His	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1	P35346
SSTR5	NM_001053.4 link	c.76A>C	p.Asn26His	missense_variant	Exon 1 of 1		NP_001044.1	P35346
SSTR5-AS1	NR_027242.1 link	n.-213T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSTR5	ENST00000689027.1 link	c.76A>C	p.Asn26His	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1	P35346
SSTR5	ENST00000293897.6 link	c.76A>C	p.Asn26His	missense_variant	Exon 1 of 1	6		ENSP00000293897.4	P35346
SSTR5-AS1	ENST00000566499.1 link	n.-237T>G		upstream_gene_variant		4
SSTR5-AS1	ENST00000624643.1 link	n.-213T>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1446450

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

718814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000843

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76A>C (p.N26H) alteration is located in exon 1 (coding exon 1) of the SSTR5 gene. This alteration results from a A to C substitution at nucleotide position 76, causing the asparagine (N) at amino acid position 26 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.30

Sift

Benign

0.035

Sift4G

Uncertain

0.055

Polyphen

0.99

Vest4

0.53

MutPred

0.30

Gain of sheet (P = 0.0344);

MVP

0.88

MPC

0.60

ClinPred

0.62

GERP RS

4.6

Varity_R

0.094

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over