15-41849902-G-A

Position:

chr15-41849902-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016642.4(SPTBN5):c.10979C>T(p.Thr3660Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000941 in 1,593,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 0 hom. )

Consequence

SPTBN5
NM_016642.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.806

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:

SPTBN5 (HGNC:):

SPTBN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0062273443).

BP6

Variant 15-41849902-G-A is Benign according to our data. Variant chr15-41849902-G-A is described in ClinVar as [Benign]. Clinvar id is 2645200.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN5	NM_016642.4 linkuse as main transcript	c.10979C>T	p.Thr3660Met	missense_variant	67/68	ENST00000320955.8	NP_057726.4	Q9NRC6
SPTBN5	XM_017022299.2 linkuse as main transcript	c.11159C>T	p.Thr3720Met	missense_variant	65/66		XP_016877788.1
SPTBN5	XM_017022302.2 linkuse as main transcript	c.8336C>T	p.Thr2779Met	missense_variant	53/54		XP_016877791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN5	ENST00000320955.8 linkuse as main transcript	c.10979C>T	p.Thr3660Met	missense_variant	67/68	1	NM_016642.4	ENSP00000317790.6		Q9NRC6
SPTBN5	ENST00000563899.1 linkuse as main transcript	n.671C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000713

AC:

154

AN:

216064

Hom.:

AF XY:

0.000771

AC XY:

AN XY:

116758

show subpopulations

Gnomad AFR exome

AF:

0.000484

Gnomad AMR exome

AF:

0.000901

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.0000524

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000729

GnomAD4 exome

AF:

0.000949

AC:

1367

AN:

1440954

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

710

AN XY:

714564

show subpopulations

Gnomad4 AFR exome

AF:

0.000302

Gnomad4 AMR exome

AF:

0.000912

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000266

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.000620

GnomAD4 genome

AF:

0.000873

AC:

133

AN:

152354

Hom.:

Cov.:

AF XY:

0.000966

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000907

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.000727

AC:

ExAC

AF:

0.000557

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.10874C>T (p.T3625M) alteration is located in exon 67 (coding exon 66) of the SPTBN5 gene. This alteration results from a C to T substitution at nucleotide position 10874, causing the threonine (T) at amino acid position 3625 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

SPTBN5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.4

DANN

Benign

0.89

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.43

M_CAP

Benign

0.021

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.39

REVEL

Benign

0.073

Sift

Uncertain

0.020

Sift4G

Uncertain

0.012

Polyphen

0.078

Vest4

0.22

MVP

0.53

ClinPred

0.0081

GERP RS

0.29

Varity_R

0.014

gMVP

0.14

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