Variant chr15-45402619-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PS1_ModeratePM2PP5_Moderate

The NM_024063.3(SPATA5L1):c.190C>T(p.Arg64Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,576,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R64Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPATA5L1
NM_024063.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.366

Variant links:

Genes affected

SPATA5L1 (HGNC:):

SPATA5L1 links:

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

AFG2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PS1

Transcript NM_024063.3 (SPATA5L1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-45402619-C-T is Pathogenic according to our data. Variant chr15-45402619-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1275865.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5L1	NM_024063.3 linkuse as main transcript	c.190C>T	p.Arg64Trp	missense_variant	1/8	ENST00000305560.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2B	ENST00000305560.11 linkuse as main transcript	c.190C>T	p.Arg64Trp	missense_variant	1/8	1	NM_024063.3	P1	Q9BVQ7-1
AFG2B	ENST00000559860.2 linkuse as main transcript	n.250C>T		non_coding_transcript_exon_variant	1/5	2
AFG2B	ENST00000531970.5 linkuse as main transcript	c.190C>T	p.Arg64Trp	missense_variant, NMD_transcript_variant	1/8	2			Q9BVQ7-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1424528

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706538

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:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Aug 27, 2021

Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -

Neurodevelopmental disorder with hearing loss and spasticity

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.97

D;D

M_CAP

Pathogenic

0.50

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

0.97

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.0

D;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.012

D;.

Sift4G

Uncertain

0.016

D;.

Polyphen

1.0

D;.

Vest4

0.64

MutPred

0.44

Loss of disorder (P = 0.0149);Loss of disorder (P = 0.0149);

MVP

0.87

MPC

1.9

ClinPred

0.99

GERP RS

4.9

Varity_R

0.35

gMVP

0.85

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