NM_015459.5:c.703C>A

Variant names:

• chr11-63644177-G-T
• NM_015459.5:c.703C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015459.5(ATL3):​c.703C>A​(p.Arg235Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATL3 NM_015459.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

Genes affected

ATL3 (HGNC:24526): (atlastin GTPase 3) This gene encodes a member of a family of dynamin-like, integral membrane GTPases. The encoded protein is required for the proper formation of the network of interconnected tubules of the endoplasmic reticulum. Mutations in this gene may be associated with hereditary sensory neuropathy type IF. Alternatively spliced transcript variants that encode distinct isoforms have been described. [provided by RefSeq, Feb 2014]

ENSG00000256789 (HGNC:58146):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL3	NM_015459.5	c.703C>A	p.Arg235Ser	missense_variant	Exon 7 of 13	ENST00000398868.8	NP_056274.3
ATL3	NM_001290048.2	c.649C>A	p.Arg217Ser	missense_variant	Exon 7 of 13		NP_001276977.1
ATL3	XM_047426725.1	c.859C>A	p.Arg287Ser	missense_variant	Exon 8 of 14		XP_047282681.1
ATL3	XM_006718493.2	c.646C>A	p.Arg216Ser	missense_variant	Exon 6 of 12		XP_006718556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8	c.703C>A	p.Arg235Ser	missense_variant	Exon 7 of 13	1	NM_015459.5	ENSP00000381844.3
ATL3	ENST00000538786.1	c.649C>A	p.Arg217Ser	missense_variant	Exon 7 of 13	2		ENSP00000437593.1
ENSG00000256789	ENST00000540307.1	n.60-6383G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450048 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721798

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.8	H;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.77
MutPred		0.65		Gain of helix (P = 0.0034);.;
MVP		0.77
MPC		1.1
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.89
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63411649;