Variant 15-41851129-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016642.4(SPTBN5):c.10765C>G(p.Leu3589Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,613,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

SPTBN5
NM_016642.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.104

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023934871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN5	NM_016642.4 linkuse as main transcript	c.10765C>G	p.Leu3589Val	missense_variant	65/68	ENST00000320955.8	NP_057726.4	Q9NRC6
SPTBN5	XM_017022299.2 linkuse as main transcript	c.10945C>G	p.Leu3649Val	missense_variant	63/66		XP_016877788.1
SPTBN5	XM_017022302.2 linkuse as main transcript	c.8122C>G	p.Leu2708Val	missense_variant	51/54		XP_016877791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN5	ENST00000320955.8 linkuse as main transcript	c.10765C>G	p.Leu3589Val	missense_variant	65/68	1	NM_016642.4	ENSP00000317790.6		Q9NRC6

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000348

AC:

AN:

247418

Hom.:

AF XY:

0.000394

AC XY:

AN XY:

134652

show subpopulations

Gnomad AFR exome

AF:

0.0000654

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.000431

AC:

630

AN:

1460866

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

314

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000480

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000459

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000580

Hom.:

Bravo

AF:

0.000820

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000358

AC:

ExAC

AF:

0.000447

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.10660C>G (p.L3554V) alteration is located in exon 65 (coding exon 64) of the SPTBN5 gene. This alteration results from a C to G substitution at nucleotide position 10660, causing the leucine (L) at amino acid position 3554 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0086

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.39

M_CAP

Benign

0.0085

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.63

REVEL

Benign

0.045

Sift

Uncertain

0.027

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.24

MVP

0.31

ClinPred

0.0091

GERP RS

2.3

Varity_R

0.059

gMVP

0.045

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

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