14-50560409-G-C

Variant names:

• chr14-50560409-G-C
• rs74885887
• NM_015915.5:c.34+110G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366
• Publications: 1 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 -20 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 VariationId is 1268055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 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.34+110G>C		intron	N/A	NP_056999.2
	ATL1	NM_001127713.1		c.34+110G>C		intron	N/A	NP_001121185.1	Q53F53
	ATL1	NM_181598.4		c.34+110G>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.34+110G>C		intron	N/A	ENSP00000351155.7	Q8WXF7-1
	ATL1	ENST00000441560.6	TSL:1	c.34+110G>C		intron	N/A	ENSP00000413675.2	Q8WXF7-2
	ATL1	ENST00000557735.2	TSL:4	c.-307G>C		5_prime_UTR	Exon 1 of 13	ENSP00000451015.2	G3V334

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

African (AFR) AF: 0.116 AC: 3345 AN: 28880

American (AMR) AF: 0.0105 AC: 373 AN: 35374

Ashkenazi Jewish (ASJ) AF: 0.00630 AC: 151 AN: 23962

East Asian (EAS) AF: 0.0643 AC: 2249 AN: 34960

South Asian (SAS) AF: 0.0212 AC: 1614 AN: 76182

European-Finnish (FIN) AF: 0.00701 AC: 323 AN: 46100

Middle Eastern (MID) AF: 0.0218 AC: 118 AN: 5422

European-Non Finnish (NFE) AF: 0.00426 AC: 4103 AN: 962622

Other (OTH) AF: 0.0182 AC: 977 AN: 53642

GnomAD4 genome AF: 0.0401 AC: 6069 AN: 151436 Hom.: 278 Cov.: 33 AF XY: 0.0399 AC XY: 2957 AN XY: 74072

African (AFR) AF: 0.115 AC: 4679 AN: 40702

American (AMR) AF: 0.0213 AC: 325 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.0640 AC: 332 AN: 5184

South Asian (SAS) AF: 0.0261 AC: 126 AN: 4834

European-Finnish (FIN) AF: 0.00762 AC: 81 AN: 10628

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00613 AC: 417 AN: 68024

Other (OTH) AF: 0.0384 AC: 81 AN: 2110

Alfa AF: 0.0274 Hom.: 21

Bravo AF: 0.0433

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.37
PromoterAI		-0.027	Neutral
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: rs74885887; hg19: chr14-51027127; COSMIC: COSV63296798;