14-50617517-T-C

Variant names:

• chr14-50617517-T-C
• rs17122693
• NM_015915.5:c.862+3006T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015915.5(ATL1):​c.862+3006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,126 control chromosomes in the GnomAD database, including 2,822 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2822 hom., cov: 32)
• Consequence: ATL1 NM_015915.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 3A

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• neuropathy, hereditary sensory, type 1D

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• hereditary sensory and autonomic neuropathy type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015915.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL1	NM_015915.5	MANE Select	c.862+3006T>C		intron	N/A	NP_056999.2
	ATL1	NM_001127713.1		c.862+3006T>C		intron	N/A	NP_001121185.1	Q53F53
	ATL1	NM_181598.4		c.862+3006T>C		intron	N/A	NP_853629.2	Q8WXF7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL1	ENST00000358385.12	TSL:1 MANE Select	c.862+3006T>C		intron	N/A	ENSP00000351155.7	Q8WXF7-1
	ATL1	ENST00000441560.6	TSL:1	c.862+3006T>C		intron	N/A	ENSP00000413675.2	Q8WXF7-2
	ATL1	ENST00000682037.1		c.862+3006T>C		intron	N/A	ENSP00000508289.1	A0A804HLC1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26803 AN: 152008 Hom.: 2822 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26824 AN: 152126 Hom.: 2822 Cov.: 32 AF XY: 0.173 AC XY: 12890 AN XY: 74388

African (AFR) AF: 0.295 AC: 12228 AN: 41458

American (AMR) AF: 0.128 AC: 1952 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3468

East Asian (EAS) AF: 0.0776 AC: 403 AN: 5192

South Asian (SAS) AF: 0.0774 AC: 373 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1442 AN: 10600

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9139 AN: 67984

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.147 Hom.: 6668

Bravo AF: 0.181

Asia WGS AF: 0.0980 AC: 340 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.70
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17122693; hg19: chr14-51084235;