15-41851335-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016642.4(SPTBN5):c.10691A>C(p.Asn3564Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,550,786 control chromosomes in the GnomAD database, including 610,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (58109 hom., cov: 29)
  • Exomes 𝑓: 0.88 (552871 hom.)
• Consequence: SPTBN5 NM_016642.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.654839E-7).
• BP6: Variant 15-41851335-T-G is Benign according to our data. Variant chr15-41851335-T-G is described in ClinVar as [Benign]. Clinvar id is 1288750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTBN5	NM_016642.4	c.10691A>C	p.Asn3564Thr	missense_variant	64/68	ENST00000320955.8
SPTBN5	XM_017022299.2	c.10871A>C	p.Asn3624Thr	missense_variant	62/66
SPTBN5	XM_017022302.2	c.8048A>C	p.Asn2683Thr	missense_variant	50/54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTBN5	ENST00000320955.8	c.10691A>C	p.Asn3564Thr	missense_variant	64/68	1	NM_016642.4	P1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131995 AN: 151856 Hom.: 58072 Cov.: 29

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.865

GnomAD3 exomes AF: 0.840 AC: 129704 AN: 154454 Hom.: 55861 AF XY: 0.845 AC XY: 69138 AN XY: 81786

Gnomad AFR exome AF: 0.864

Gnomad AMR exome AF: 0.760

Gnomad ASJ exome AF: 0.875

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.874

Gnomad FIN exome AF: 0.914

Gnomad NFE exome AF: 0.908

Gnomad OTH exome AF: 0.871

GnomAD4 exome AF: 0.885 AC: 1237319 AN: 1398812 Hom.: 552871 Cov.: 58 AF XY: 0.885 AC XY: 610305 AN XY: 689930

Gnomad4 AFR exome AF: 0.864

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.876

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.873

Gnomad4 FIN exome AF: 0.910

Gnomad4 NFE exome AF: 0.906

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.869 AC: 132079 AN: 151974 Hom.: 58109 Cov.: 29 AF XY: 0.867 AC XY: 64364 AN XY: 74266

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.865

Alfa AF: 0.889 Hom.: 90283

Bravo AF: 0.856

TwinsUK AF: 0.905 AC: 3355

ALSPAC AF: 0.910 AC: 3508

ESP6500AA AF: 0.885 AC: 3231

ESP6500EA AF: 0.920 AC: 6899

ExAC AF: 0.834 AC: 36215

Asia WGS AF: 0.687 AC: 2392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.0080
Dann	Benign	0.41
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	9.7e-7	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.015
Sift	Benign	0.69	T
Sift4G	Benign	1.0	T
Vest4		0.021
ClinPred		0.0020	T
GERP RS		-1.3
Varity_R		0.031
gMVP		0.059

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

Other links and lift over

dbSNP: rs1197665; hg19: chr15-42143533; COSMIC: COSV58018337; COSMIC: COSV58018337;