Variant chr15-41850879-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016642.4(SPTBN5):c.10896G>A(p.Trp3632*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,602,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

SPTBN5
NM_016642.4 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.04

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN5	NM_016642.4 linkuse as main transcript	c.10896G>A	p.Trp3632*	stop_gained	66/68	ENST00000320955.8	NP_057726.4	Q9NRC6
SPTBN5	XM_017022299.2 linkuse as main transcript	c.11076G>A	p.Trp3692*	stop_gained	64/66		XP_016877788.1
SPTBN5	XM_017022302.2 linkuse as main transcript	c.8253G>A	p.Trp2751*	stop_gained	52/54		XP_016877791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN5	ENST00000320955.8 linkuse as main transcript	c.10896G>A	p.Trp3632*	stop_gained	66/68	1	NM_016642.4	ENSP00000317790.6		Q9NRC6

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000200

AC:

AN:

230238

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

125090

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000499

Gnomad NFE exome

AF:

0.000356

Gnomad OTH exome

AF:

0.000705

GnomAD4 exome

AF:

0.000216

AC:

313

AN:

1450526

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

146

AN XY:

720400

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000155

Gnomad4 NFE exome

AF:

0.000254

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.000302

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Feb 27, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Benign

0.97

Eigen

Benign

0.091

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.22

Vest4

0.089

GERP RS

2.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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