chr14-50560407-AC-A

Variant names:

• chr14-50560407-AC-A
• rs200164458
• NM_015915.5:c.34+109delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015915.5(ATL1):​c.34+109delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000742 in 1,429,078 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (3 hom.)
• Consequence: ATL1 NM_015915.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.296
• Publications: 0 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]

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-50560407-AC-A is Benign according to our data. Variant chr14-50560407-AC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1190758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00351 (535/152340) while in subpopulation AFR AF = 0.0122 (507/41576). AF 95% confidence interval is 0.0113. There are 3 homozygotes in GnomAd4. There are 254 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 535 AD,SD gene.

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.34+109delC		intron	N/A	NP_056999.2
	ATL1	NM_001127713.1		c.34+109delC		intron	N/A	NP_001121185.1	Q53F53
	ATL1	NM_181598.4		c.34+109delC		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.34+109delC		intron	N/A	ENSP00000351155.7	Q8WXF7-1
	ATL1	ENST00000441560.6	TSL:1	c.34+109delC		intron	N/A	ENSP00000413675.2	Q8WXF7-2
	ATL1	ENST00000557735.2	TSL:4	c.-308delC		5_prime_UTR	Exon 1 of 13	ENSP00000451015.2	G3V334

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 530 AN: 152222 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000411 AC: 525 AN: 1276738 Hom.: 3 Cov.: 18 AF XY: 0.000338 AC XY: 215 AN XY: 635282

African (AFR) AF: 0.0137 AC: 400 AN: 29246

American (AMR) AF: 0.000537 AC: 19 AN: 35414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24050

East Asian (EAS) AF: 0.00 AC: 0 AN: 35070

South Asian (SAS) AF: 0.0000524 AC: 4 AN: 76380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46226

Middle Eastern (MID) AF: 0.000554 AC: 3 AN: 5412

European-Non Finnish (NFE) AF: 0.0000474 AC: 46 AN: 970952

Other (OTH) AF: 0.000982 AC: 53 AN: 53988

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152340 Hom.: 3 Cov.: 32 AF XY: 0.00341 AC XY: 254 AN XY: 74496

African (AFR) AF: 0.0122 AC: 507 AN: 41576

American (AMR) AF: 0.00111 AC: 17 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68004

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00419

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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: rs200164458; hg19: chr14-51027125;