20-23036445-T-C

Variant names:

• chr20-23036445-T-C
• rs2567608
• NM_001052.4:c.962T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001052.4(SSTR4):​c.962T>C​(p.Phe321Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,613,532 control chromosomes in the GnomAD database, including 177,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.48 (17821 hom., cov: 32)
  • Exomes 𝑓: 0.46 (159502 hom.)
• Consequence: SSTR4 NM_001052.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

SSTR4 (HGNC:11333): (somatostatin receptor 4) Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biologic effects of somatostatin are probably mediated by a family of G protein-coupled receptors that are expressed in a tissue-specific manner. SSTR4 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in fetal and adult brain and lung. [provided by RefSeq, Jul 2008]

ENSG00000234646 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.6383345E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR4	NM_001052.4	c.962T>C	p.Phe321Ser	missense_variant	Exon 1 of 1	ENST00000255008.5	NP_001043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSTR4	ENST00000255008.5	c.962T>C	p.Phe321Ser	missense_variant	Exon 1 of 1	6	NM_001052.4	ENSP00000255008.3
ENSG00000234646	ENST00000440921.6	n.827-1778T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73173 AN: 151902 Hom.: 17802 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.489

GnomAD3 exomes AF: 0.485 AC: 121010 AN: 249304 Hom.: 29861 AF XY: 0.489 AC XY: 66039 AN XY: 135104

Gnomad AFR exome AF: 0.530

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.597

Gnomad EAS exome AF: 0.559

Gnomad SAS exome AF: 0.576

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.464 AC: 678788 AN: 1461512 Hom.: 159502 Cov.: 73 AF XY: 0.468 AC XY: 340069 AN XY: 727048

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.564

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.482 AC: 73239 AN: 152020 Hom.: 17821 Cov.: 32 AF XY: 0.485 AC XY: 36040 AN XY: 74320

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.492

Alfa AF: 0.461 Hom.: 22631

Bravo AF: 0.486

TwinsUK AF: 0.449 AC: 1664

ALSPAC AF: 0.432 AC: 1666

ESP6500AA AF: 0.509 AC: 2237

ESP6500EA AF: 0.455 AC: 3917

ExAC AF: 0.482 AC: 58561

Asia WGS AF: 0.572 AC: 1990 AN: 3478

EpiCase AF: 0.462

EpiControl AF: 0.473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.025
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.75
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00096	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.000076	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.97	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	4.8	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.77
ClinPred		0.0012	T
GERP RS		3.6
Varity_R		0.044
gMVP		0.25

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: rs2567608; hg19: chr20-23017082; COSMIC: COSV54797319; COSMIC: COSV54797319;