16-1078894-C-T

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.26C>T(p.Thr9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,606,448 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T9A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (4 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38

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=0.004814476).
• BP6: Variant 16-1078894-C-T is Benign according to our data. Variant chr16-1078894-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 347 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSTR5	NM_001172560.3	c.26C>T	p.Thr9Met	missense_variant	2/2	ENST00000689027.1
SSTR5	NM_001053.4	c.26C>T	p.Thr9Met	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSTR5	ENST00000689027.1	c.26C>T	p.Thr9Met	missense_variant	2/2		NM_001172560.3	P1
SSTR5	ENST00000293897.7	c.26C>T	p.Thr9Met	missense_variant	1/1			P1
SSTR5	ENST00000711615.1	c.26C>T	p.Thr9Met	missense_variant	2/2			P1
SSTR5	ENST00000711616.1	c.26C>T	p.Thr9Met	missense_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.00228 AC: 347 AN: 152194 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00981

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00136 AC: 318 AN: 234020 Hom.: 1 AF XY: 0.00119 AC XY: 154 AN XY: 129006

Gnomad AFR exome AF: 0.00276

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00114

Gnomad EAS exome AF: 0.00140

Gnomad SAS exome AF: 0.000299

Gnomad FIN exome AF: 0.000116

Gnomad NFE exome AF: 0.000914

Gnomad OTH exome AF: 0.00190

GnomAD4 exome AF: 0.000787 AC: 1144 AN: 1454138 Hom.: 4 Cov.: 29 AF XY: 0.000732 AC XY: 530 AN XY: 723562

Gnomad4 AFR exome AF: 0.00314

Gnomad4 AMR exome AF: 0.00390

Gnomad4 ASJ exome AF: 0.000614

Gnomad4 EAS exome AF: 0.000732

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.0000418

Gnomad4 NFE exome AF: 0.000598

Gnomad4 OTH exome AF: 0.00201

GnomAD4 genome AF: 0.00228 AC: 348 AN: 152310 Hom.: 4 Cov.: 33 AF XY: 0.00240 AC XY: 179 AN XY: 74482

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.00980

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.00276

ESP6500AA AF: 0.00163 AC: 7

ESP6500EA AF: 0.000707 AC: 6

ExAC AF: 0.00104 AC: 124

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.00125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	4.7
Dann	Benign	0.90
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.14
Sift	Benign	0.19	T
Sift4G	Benign	0.17	T
Polyphen		0.66	P
Vest4		0.10
MVP		0.41
MPC		0.23
ClinPred		0.0028	T
GERP RS		-6.4
Varity_R		0.015
gMVP		0.39

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: rs143790659; hg19: chr16-1128894; COSMIC: COSV99036531; COSMIC: COSV99036531;