Variant 10-115093802-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207303.4(ATRNL1):c.52G>A(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,470,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ATRNL1
NM_207303.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

ATRNL1 (HGNC:29063): (attractin like 1) Predicted to enable carbohydrate binding activity. Predicted to be involved in several processes, including animal organ morphogenesis; cell migration; and substrate adhesion-dependent cell spreading. Predicted to act upstream of or within G protein-coupled receptor signaling pathway. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be active in basement membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATRNL1 links:

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ACMG classification

Classification made for transcript

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=0.073283106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRNL1	NM_207303.4 linkuse as main transcript	c.52G>A	p.Gly18Arg	missense_variant	1/29	ENST00000355044.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRNL1	ENST00000355044.8 linkuse as main transcript	c.52G>A	p.Gly18Arg	missense_variant	1/29	1	NM_207303.4	P1	Q5VV63-1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1318006

Hom.:

Cov.:

AF XY:

0.00000928

AC XY:

AN XY:

646830

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000158

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:

0.00

Gnomad4 OTH exome

AF:

0.000110

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000329

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.52G>A (p.G18R) alteration is located in exon 1 (coding exon 1) of the ATRNL1 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0050

.;T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.;N

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.11

.;.;N

REVEL

Benign

0.064

Sift

Benign

0.52

.;.;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.060

B;.;B

Vest4

0.13

MutPred

0.29

Gain of MoRF binding (P = 0.0142);Gain of MoRF binding (P = 0.0142);Gain of MoRF binding (P = 0.0142);

MVP

0.043

MPC

0.88

ClinPred

0.59

GERP RS

3.3

Varity_R

0.060

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over