chr11-63636274-G-C

Position:

• chr11-63636274-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015459.5(ATL3):​c.911C>G​(p.Ser304Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 30)
• Consequence: ATL3 NM_015459.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17068097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATL3	NM_015459.5	c.911C>G	p.Ser304Cys	missense_variant	9/13	ENST00000398868.8	NP_056274.3
ATL3	NM_001290048.2	c.857C>G	p.Ser286Cys	missense_variant	9/13		NP_001276977.1
ATL3	XM_047426725.1	c.1067C>G	p.Ser356Cys	missense_variant	10/14		XP_047282681.1
ATL3	XM_006718493.2	c.854C>G	p.Ser285Cys	missense_variant	8/12		XP_006718556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8	c.911C>G	p.Ser304Cys	missense_variant	9/13	1	NM_015459.5	ENSP00000381844.3
ATL3	ENST00000538786.1	c.857C>G	p.Ser286Cys	missense_variant	9/13	2		ENSP00000437593.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.059
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.15	B;.
Vest4		0.21
MutPred		0.37		Loss of disorder (P = 0.0088);.;
MVP		0.82
MPC		0.66
ClinPred		0.93	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757344746; hg19: chr11-63403746;