14-50632151-A-G

Position:

• chr14-50632151-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000555720.5(SAV1):​c.*2002T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 858,970 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (11 hom.)
• Consequence: SAV1 ENST00000555720.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00100

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=-0.86).
• BP6: Variant 14-50632151-A-G is Benign according to our data. Variant chr14-50632151-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1204485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1626/152336) while in subpopulation AFR AF= 0.0357 (1485/41570). AF 95% confidence interval is 0.0342. There are 26 homozygotes in gnomad4. There are 794 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1626 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATL1	NM_015915.5	c.1567-78A>G		intron_variant		ENST00000358385.12	NP_056999.2
ATL1	NM_001127713.1	c.1552-78A>G		intron_variant			NP_001121185.1
ATL1	NM_181598.4	c.1552-78A>G		intron_variant			NP_853629.2
ATL1	XM_047431430.1	c.1567-78A>G		intron_variant			XP_047287386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL1	ENST00000358385.12	c.1567-78A>G		intron_variant		1	NM_015915.5	ENSP00000351155.7

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1622 AN: 152218 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00693

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00107 AC: 757 AN: 706634 Hom.: 11 Cov.: 9 AF XY: 0.000847 AC XY: 315 AN XY: 371864

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.00211

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000172

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000812

Gnomad4 OTH exome AF: 0.00286

GnomAD4 genome AF: 0.0107 AC: 1626 AN: 152336 Hom.: 26 Cov.: 32 AF XY: 0.0107 AC XY: 794 AN XY: 74494

Gnomad4 AFR AF: 0.0357

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00565 Hom.: 0

Bravo AF: 0.0122

Asia WGS AF: 0.00289 AC: 10 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.82
DANN	Benign	0.42

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: rs113367786; hg19: chr14-51098869;