dbSNP rs770538531: ATL1:p.Asn318Ser (chr14-50620689-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_015915.5(ATL1):c.953A>G(p.Asn318Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ATL1
NM_015915.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.88

Variant links:

Genes affected

ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the ATL1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 60 curated pathogenic missense variants (we use a threshold of 10). The gene has 10 curated benign missense variants. Gene score misZ: 2.6313 (below the threshold of 3.09). Trascript score misZ: 3.8383 (above the threshold of 3.09). GenCC associations: The gene is linked to hereditary sensory and autonomic neuropathy type 1, hereditary spastic paraplegia 3A, neuropathy, hereditary sensory, type 1D.

BP4

Computational evidence support a benign effect (MetaRNN=0.13895687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL1	NM_015915.5 link	c.953A>G	p.Asn318Ser	missense_variant	Exon 9 of 14	ENST00000358385.12	NP_056999.2	Q8WXF7-1A0A0S2Z5B0Q53F53
ATL1	NM_001127713.1 link	c.953A>G	p.Asn318Ser	missense_variant	Exon 10 of 14		NP_001121185.1	Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1	NM_181598.4 link	c.953A>G	p.Asn318Ser	missense_variant	Exon 9 of 13		NP_853629.2	Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1	XM_047431430.1 link	c.953A>G	p.Asn318Ser	missense_variant	Exon 10 of 15		XP_047287386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL1	ENST00000358385.12 link	c.953A>G	p.Asn318Ser	missense_variant	Exon 9 of 14	1	NM_015915.5	ENSP00000351155.7		Q8WXF7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727070

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.077

.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

-0.79

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.050

N;N

REVEL

Uncertain

0.36

Sift

Benign

1.0

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.0

.;B

Vest4

0.094

MutPred

0.36

Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);

MVP

0.71

MPC

0.52

ClinPred

0.75

GERP RS

5.8

Varity_R

0.51

gMVP

0.14

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over