Variant chr5-169594221-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017785.5(SPDL1):c.608G>T(p.Arg203Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,613,840 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R203G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 3 hom. )

Consequence

SPDL1
NM_017785.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

Variant links:

Genes affected

SPDL1 (HGNC:26010): (spindle apparatus coiled-coil protein 1) This gene encodes a coiled-coil domain-containing protein that functions in mitotic spindle formation and chromosome segregation. The encoded protein plays a role in coordinating microtubule attachment by promoting recruitment of dynein proteins, and in mitotic checkpoint signaling. [provided by RefSeq, Jul 2016]

SPDL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06698945).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPDL1	NM_017785.5 linkuse as main transcript	c.608G>T	p.Arg203Leu	missense_variant	5/12	ENST00000265295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPDL1	ENST00000265295.9 linkuse as main transcript	c.608G>T	p.Arg203Leu	missense_variant	5/12	1	NM_017785.5	P1	Q96EA4-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000442

AC:

111

AN:

251094

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000811

AC:

1185

AN:

1461592

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

581

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000987

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000401

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000710

Hom.:

Bravo

AF:

0.000393

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000711

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

Sep 26, 2022

The c.608G>T (p.R203L) alteration is located in exon 5 (coding exon 4) of the SPDL1 gene. This alteration results from a G to T substitution at nucleotide position 608, causing the arginine (R) at amino acid position 203 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;T

Eigen

Benign

0.089

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.65

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.063

Sift

Benign

0.050

D;D

Sift4G

Benign

0.22

T;T

Polyphen

0.80

P;.

Vest4

0.56

MVP

0.69

MPC

0.18

ClinPred

0.038

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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