rs796051895

Positions:

• chr4-122929049-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_145207.3(AFG2A):​c.298G>A​(p.Ala100Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AFG2A NM_145207.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.16

Genes affected

AFG2A (HGNC:18119): (AFG2 AAA ATPase homolog A) This gene encodes a member of the ATPase associated with diverse activities family, whose members are defined by a highly conserved ATPase domain. Members of this family participate in diverse cellular processes that include membrane fusion, DNA replication, microtubule severing, and protein degradation. The protein encoded by this gene has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Allelic variants in this gene have been associated with epilepsy, hearing loss, and cognitive disability syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

SPATA5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-122929049-G-A is Pathogenic according to our data. Variant chr4-122929049-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 203536.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-122929049-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFG2A	NM_145207.3	c.298G>A	p.Ala100Thr	missense_variant	3/16	ENST00000274008.5	NP_660208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA5	ENST00000274008.5	c.298G>A	p.Ala100Thr	missense_variant	3/16	1	NM_145207.3	ENSP00000274008.3
SPATA5	ENST00000422835.2	n.340G>A		non_coding_transcript_exon_variant	3/15	1
SPATA5	ENST00000675612.1	c.295G>A	p.Ala99Thr	missense_variant	3/17			ENSP00000502453.1
SPATA5	ENST00000674886.1	n.360G>A		non_coding_transcript_exon_variant	3/11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.041	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.46	D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.54
MutPred		0.27		Gain of glycosylation at Y98 (P = 0.017);
MVP		0.91
MPC		0.62
ClinPred		0.96	D
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.36
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs796051895; hg19: chr4-123850204;