Genetic Variant NM_001052.4:c.962T>C (chr20-23036445-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 17821 hom., cov: 32)

Exomes 𝑓: 0.46 ( 159502 hom. )

Consequence

SSTR4
NM_001052.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

47 publications found

Variant links:

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]

SSTR4 links:

ENSG00000234646 (HGNC:):

ENSG00000234646 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.962T>C	p.Phe321Ser	missense_variant	Exon 1 of 1	ENST00000255008.5	NP_001043.2	P31391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSTR4	ENST00000255008.5 link	c.962T>C	p.Phe321Ser	missense_variant	Exon 1 of 1	6	NM_001052.4	ENSP00000255008.3		P31391
ENSG00000234646	ENST00000440921.6 link	n.827-1778T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73173

AN:

151902

Hom.:

17802

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.485

AC:

121010

AN:

249304

AF XY:

0.489

show subpopulations

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 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.:

AF XY:

0.468

AC XY:

340069

AN XY:

727048

show subpopulations

African (AFR)

AF:

0.532

AC:

17803

AN:

33480

American (AMR)

AF:

0.482

AC:

21549

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

15526

AN:

26104

East Asian (EAS)

AF:

0.564

AC:

22390

AN:

39694

South Asian (SAS)

AF:

0.573

AC:

49434

AN:

86210

European-Finnish (FIN)

AF:

0.410

AC:

21907

AN:

53380

Middle Eastern (MID)

AF:

0.578

AC:

3333

AN:

5768

European-Non Finnish (NFE)

AF:

0.448

AC:

497722

AN:

1111802

Other (OTH)

AF:

0.482

AC:

29124

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

24484

48969

73453

97938

122422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15218

30436

45654

60872

76090

<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

AF:

0.482

AC:

73239

AN:

152020

Hom.:

17821

Cov.:

AF XY:

0.485

AC XY:

36040

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.524

AC:

21699

AN:

41446

American (AMR)

AF:

0.477

AC:

7289

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

2111

AN:

3466

East Asian (EAS)

AF:

0.554

AC:

2852

AN:

5152

South Asian (SAS)

AF:

0.591

AC:

2848

AN:

4816

European-Finnish (FIN)

AF:

0.410

AC:

4339

AN:

10584

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30582

AN:

67958

Other (OTH)

AF:

0.492

AC:

1040

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1993

3986

5978

7971

9964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.467

Hom.:

33995

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.027

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00096

LIST_S2

Benign

0.52

MetaRNN

Benign

0.000076

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.97

PhyloP100

1.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

4.8

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MPC

0.77

ClinPred

0.0012

GERP RS

3.6

Varity_R

0.044

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over