Variant 15-41851092-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_016642.4(SPTBN5):c.10802G>A(p.Gly3601Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SPTBN5
NM_016642.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.242

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=0.069716156).

BP6

Variant 15-41851092-C-T is Benign according to our data. Variant chr15-41851092-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2617708.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.10802G>A	p.Gly3601Asp	missense_variant	65/68	ENST00000320955.8	NP_057726.4	Q9NRC6
SPTBN5	XM_017022299.2 linkuse as main transcript	c.10982G>A	p.Gly3661Asp	missense_variant	63/66		XP_016877788.1
SPTBN5	XM_017022302.2 linkuse as main transcript	c.8159G>A	p.Gly2720Asp	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.10802G>A	p.Gly3601Asp	missense_variant	65/68	1	NM_016642.4	ENSP00000317790.6		Q9NRC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247120

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460652

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.37

DANN

Benign

0.57

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.34

M_CAP

Benign

0.0028

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

1.8

REVEL

Benign

0.012

Sift

Benign

0.87

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.14

MutPred

0.46

Loss of methylation at R3600 (P = 0.0346);

MVP

0.14

ClinPred

0.032

GERP RS

0.80

Varity_R

0.027

gMVP

0.054

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