Variant 15-41850920-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016642.4(SPTBN5):c.10855A>G(p.Ile3619Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 1,598,290 control chromosomes in the GnomAD database, including 2,209 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 146 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2063 hom. )

Consequence

SPTBN5
NM_016642.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.217

Variant links:

Genes affected

SPTBN5 (HGNC:15680): (spectrin beta, non-erythrocytic 5) Enables several functions, including cytoskeletal protein binding activity; dynein intermediate chain binding activity; and identical protein binding activity. Acts upstream of or within Golgi organization and lysosomal transport. Located in cytoplasm; photoreceptor connecting cilium; and photoreceptor disc membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPTBN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064282715).

BP6

Variant 15-41850920-T-C is Benign according to our data. Variant chr15-41850920-T-C is described in ClinVar as [Benign]. Clinvar id is 3057154.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPTBN5	NM_016642.4 linkuse as main transcript	c.10855A>G	p.Ile3619Val	missense_variant	66/68	ENST00000320955.8
SPTBN5	XM_017022299.2 linkuse as main transcript	c.11035A>G	p.Ile3679Val	missense_variant	64/66
SPTBN5	XM_017022302.2 linkuse as main transcript	c.8212A>G	p.Ile2738Val	missense_variant	52/54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTBN5	ENST00000320955.8 linkuse as main transcript	c.10855A>G	p.Ile3619Val	missense_variant	66/68	1	NM_016642.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5275

AN:

146830

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0168

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00690

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0559

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0347

AC:

7972

AN:

229498

Hom.:

184

AF XY:

0.0352

AC XY:

4385

AN XY:

124606

show subpopulations

Gnomad AFR exome

AF:

0.00904

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.0000590

Gnomad SAS exome

AF:

0.00834

Gnomad FIN exome

AF:

0.0480

Gnomad NFE exome

AF:

0.0531

Gnomad OTH exome

AF:

0.0418

GnomAD4 exome

AF:

0.0495

AC:

71816

AN:

1451344

Hom.:

2063

Cov.:

AF XY:

0.0482

AC XY:

34760

AN XY:

720838

show subpopulations

Gnomad4 AFR exome

AF:

0.00788

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.00886

Gnomad4 FIN exome

AF:

0.0475

Gnomad4 NFE exome

AF:

0.0579

Gnomad4 OTH exome

AF:

0.0431

GnomAD4 genome

AF:

0.0359

AC:

5277

AN:

146946

Hom.:

146

Cov.:

AF XY:

0.0349

AC XY:

2507

AN XY:

71750

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00691

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.0559

Gnomad4 OTH

AF:

0.0349

Alfa

AF:

0.0473

Hom.:

222

Bravo

AF:

0.0328

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0522

AC:

201

ESP6500AA

AF:

0.0115

AC:

ESP6500EA

AF:

0.0499

AC:

426

ExAC

AF:

0.0319

AC:

3850

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SPTBN5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.70

Cadd

Benign

0.67

Dann

Benign

0.69

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.33

REVEL

Benign

0.012

Sift

Benign

0.47

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.063

ClinPred

0.0033

GERP RS

0.88

Varity_R

0.042

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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