Variant 15-41850931-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016642.4(SPTBN5):c.10844G>C(p.Ser3615Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,348 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SPTBN5
NM_016642.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.236

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11394295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN5	NM_016642.4 linkuse as main transcript	c.10844G>C	p.Ser3615Thr	missense_variant	66/68	ENST00000320955.8	NP_057726.4	Q9NRC6
SPTBN5	XM_017022299.2 linkuse as main transcript	c.11024G>C	p.Ser3675Thr	missense_variant	64/66		XP_016877788.1
SPTBN5	XM_017022302.2 linkuse as main transcript	c.8201G>C	p.Ser2734Thr	missense_variant	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.10844G>C	p.Ser3615Thr	missense_variant	66/68	1	NM_016642.4	ENSP00000317790.6		Q9NRC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450348

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720254

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 25, 2023

The c.10739G>C (p.S3580T) alteration is located in exon 66 (coding exon 65) of the SPTBN5 gene. This alteration results from a G to C substitution at nucleotide position 10739, causing the serine (S) at amino acid position 3580 to be replaced by a threonine (T). 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

0.096

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.2

DANN

Benign

0.65

DEOGEN2

Benign

0.010

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.32

M_CAP

Benign

0.0033

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

REVEL

Benign

0.025

Sift

Benign

0.22

Sift4G

Uncertain

0.014

Polyphen

0.42

Vest4

0.22

MutPred

0.46

Loss of glycosylation at S3615 (P = 0.0359);

MVP

0.48

ClinPred

0.057

GERP RS

1.2

Varity_R

0.071

gMVP

0.081

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over