chr14-50560409-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015915.5(ATL1):​c.34+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,267,266 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: ATL1 NM_015915.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

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>A		intron	N/A	NP_056999.2
	ATL1	NM_001127713.1		c.34+110G>A		intron	N/A	NP_001121185.1	Q53F53
	ATL1	NM_181598.4		c.34+110G>A		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>A		intron	N/A	ENSP00000351155.7	Q8WXF7-1
	ATL1	ENST00000441560.6	TSL:1	c.34+110G>A		intron	N/A	ENSP00000413675.2	Q8WXF7-2
	ATL1	ENST00000557735.2	TSL:4	c.-307G>A		5_prime_UTR	Exon 1 of 13	ENSP00000451015.2	G3V334

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.89e-7 AC: 1 AN: 1267266 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 630824

African (AFR) AF: 0.00 AC: 0 AN: 28912

American (AMR) AF: 0.00 AC: 0 AN: 35376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23964

East Asian (EAS) AF: 0.00 AC: 0 AN: 34972

South Asian (SAS) AF: 0.00 AC: 0 AN: 76194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5422

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 962664

Other (OTH) AF: 0.00 AC: 0 AN: 53658

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		0.37
PromoterAI		-0.058	Neutral

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;