Variant chr15-45402676-G-A 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_024063.3(SPATA5L1):c.247G>A(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.0e-7 ( 0 hom. )

Consequence

SPATA5L1
NM_024063.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.541

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:

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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=0.085867256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA5L1	NM_024063.3 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/8	ENST00000305560.11	NP_076968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFG2B	ENST00000305560.11 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/8	1	NM_024063.3	ENSP00000305494	P1	Q9BVQ7-1
AFG2B	ENST00000559860.2 linkuse as main transcript	n.307G>A		non_coding_transcript_exon_variant	1/5	2
AFG2B	ENST00000531970.5 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant, NMD_transcript_variant	1/8	2		ENSP00000436823		Q9BVQ7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000552

AC:

AN:

181308

Hom.:

AF XY:

0.00

AC XY:

AN XY:

100752

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706566

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:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.247G>A (p.A83T) alteration is located in exon 1 (coding exon 1) of the SPATA5L1 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the alanine (A) at amino acid position 83 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

0.088

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.2

DANN

Benign

0.90

DEOGEN2

Benign

0.0072

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.56

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.59

N;.

REVEL

Benign

0.17

Sift

Benign

0.40

T;.

Sift4G

Benign

0.38

T;.

Polyphen

0.0

B;.

Vest4

0.029

MutPred

0.21

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.61

MPC

0.92

ClinPred

0.055

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.54

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