Variant chr14-50560409-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015915.5(ATL1):c.34+110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,418,580 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 278 hom., cov: 33)

Exomes 𝑓: 0.010 ( 354 hom. )

Consequence

ATL1
NM_015915.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.366

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:

MAP4K5 (HGNC:6867): (mitogen-activated protein kinase kinase kinase kinase 5) This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

MAP4K5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 14-50560409-G-C is Benign according to our data. Variant chr14-50560409-G-C is described in ClinVar as [Benign]. Clinvar id is 1268055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATL1	NM_015915.5 linkuse as main transcript	c.34+110G>C		intron_variant		ENST00000358385.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATL1	ENST00000358385.12 linkuse as main transcript	c.34+110G>C		intron_variant		1	NM_015915.5	P3	Q8WXF7-1

Frequencies

GnomAD3 genomes

AF:

0.0400

AC:

6051

AN:

151328

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.0639

Gnomad SAS

AF:

0.0258

Gnomad FIN

AF:

0.00762

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00613

Gnomad OTH

AF:

0.0388

GnomAD4 exome

AF:

0.0105

AC:

13253

AN:

1267144

Hom.:

354

Cov.:

AF XY:

0.0105

AC XY:

6608

AN XY:

630758

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.00630

Gnomad4 EAS exome

AF:

0.0643

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.00701

Gnomad4 NFE exome

AF:

0.00426

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0401

AC:

6069

AN:

151436

Hom.:

278

Cov.:

AF XY:

0.0399

AC XY:

2957

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.0640

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.00762

Gnomad4 NFE

AF:

0.00613

Gnomad4 OTH

AF:

0.0384

Alfa

AF:

0.0274

Hom.:

Bravo

AF:

0.0433

Asia WGS

AF:

0.0590

AC:

203

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.79

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