chr14-50632152-C-A

Position:

• chr14-50632152-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000555720.5(SAV1):​c.*2001G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 923,784 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (188 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (76 hom.)
• Consequence: SAV1 ENST00000555720.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06

Genes affected

SAV1 (HGNC:17795): (salvador family WW domain containing protein 1) WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein with two WW domains, a SARAH domain, and a coiled-coil region and is ubiquitously expressed in adult tissues. This protein binds to MST1 (mammalian sterile 20-like kinase 1) and promotes MST1-induced apoptosis. It has also been shown to bind to HAX1 (hematopoietic cell-specific protein 1 (HS1)-associated protein X-1) and to attenuate the anti-apoptotic effects of HAX1. Studies in human and mouse suggest this gene acts as a tumor suppressor. [provided by RefSeq, Aug 2012]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-50632152-C-A is Benign according to our data. Variant chr14-50632152-C-A is described in ClinVar as [Benign]. Clinvar id is 675718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATL1	NM_015915.5	c.1567-77C>A		intron_variant		ENST00000358385.12	NP_056999.2
ATL1	NM_001127713.1	c.1552-77C>A		intron_variant			NP_001121185.1
ATL1	NM_181598.4	c.1552-77C>A		intron_variant			NP_853629.2
ATL1	XM_047431430.1	c.1567-77C>A		intron_variant			XP_047287386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL1	ENST00000358385.12	c.1567-77C>A		intron_variant		1	NM_015915.5	ENSP00000351155.7

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4002 AN: 151884 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00434

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00308 AC: 2375 AN: 771782 Hom.: 76 Cov.: 10 AF XY: 0.00257 AC XY: 1035 AN XY: 402038

Gnomad4 AFR exome AF: 0.0868

Gnomad4 AMR exome AF: 0.00691

Gnomad4 ASJ exome AF: 0.00523

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000474

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000439

Gnomad4 OTH exome AF: 0.00761

GnomAD4 genome AF: 0.0264 AC: 4008 AN: 152002 Hom.: 188 Cov.: 32 AF XY: 0.0247 AC XY: 1835 AN XY: 74312

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.00434

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.000508 Hom.: 0

Bravo AF: 0.0291

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.49

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: rs75154648; hg19: chr14-51098870;