14-50560409-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.366

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.34+110G>C		intron_variant		ENST00000358385.12

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6051 AN: 151328 Hom.: 278 Cov.: 33

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.: 18 AF XY: 0.0105 AC XY: 6608 AN XY: 630758

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.: 33 AF XY: 0.0399 AC XY: 2957 AN XY: 74072

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.: 21

Bravo AF: 0.0433

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs74885887; hg19: chr14-51027127; COSMIC: COSV63296798;