16-1078908-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001172560.3(SSTR5):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,605,514 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065477192).
• BP6: Variant 16-1078908-G-A is Benign according to our data. Variant chr16-1078908-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2353937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSTR5	NM_001172560.3	c.40G>A	p.Ala14Thr	missense_variant	2/2	ENST00000689027.1
SSTR5	NM_001053.4	c.40G>A	p.Ala14Thr	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSTR5	ENST00000689027.1	c.40G>A	p.Ala14Thr	missense_variant	2/2		NM_001172560.3	P1
SSTR5	ENST00000293897.7	c.40G>A	p.Ala14Thr	missense_variant	1/1			P1
SSTR5	ENST00000711615.1	c.40G>A	p.Ala14Thr	missense_variant	2/2			P1
SSTR5	ENST00000711616.1	c.40G>A	p.Ala14Thr	missense_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.000743 AC: 113 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000688 AC: 159 AN: 231232 Hom.: 0 AF XY: 0.000730 AC XY: 93 AN XY: 127462

Gnomad AFR exome AF: 0.000508

Gnomad AMR exome AF: 0.000590

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00147

Gnomad SAS exome AF: 0.0000670

Gnomad FIN exome AF: 0.0000579

Gnomad NFE exome AF: 0.000947

Gnomad OTH exome AF: 0.000872

GnomAD4 exome AF: 0.00107 AC: 1557 AN: 1453246 Hom.: 2 Cov.: 29 AF XY: 0.00103 AC XY: 746 AN XY: 723000

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.000540

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000607

Gnomad4 SAS exome AF: 0.0000816

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.000742 AC: 113 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74462

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.000842

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000694 AC: 3

ESP6500EA AF: 0.000941 AC: 8

ExAC AF: 0.000468 AC: 56

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	0.22
Dann	Benign	0.80
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0065	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.10
Sift	Benign	0.83	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.046
MVP		0.43
MPC		0.21
ClinPred		0.0023	T
GERP RS		-3.9
Varity_R		0.030
gMVP		0.32

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

Other links and lift over

dbSNP: rs146894362; hg19: chr16-1128908;