Variant chr10-115160048-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_207303.4(ATRNL1):c.838T>C(p.Cys280Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ATRNL1
NM_207303.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRNL1	NM_207303.4 linkuse as main transcript	c.838T>C	p.Cys280Arg	missense_variant	6/29	ENST00000355044.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRNL1	ENST00000355044.8 linkuse as main transcript	c.838T>C	p.Cys280Arg	missense_variant	6/29	1	NM_207303.4	P1	Q5VV63-1
	ENST00000648967.1 linkuse as main transcript	n.818-30935A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1453960

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723094

show subpopulations

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:

0.00000361

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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

Apr 07, 2022

The c.838T>C (p.C280R) alteration is located in exon 6 (coding exon 6) of the ATRNL1 gene. This alteration results from a T to C substitution at nucleotide position 838, causing the cysteine (C) at amino acid position 280 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.55

BayesDel_noAF

Pathogenic

0.55

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

.;T;T;D

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Pathogenic

0.55

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Pathogenic

0.99

MutationAssessor

Uncertain

2.2

M;.;.;M

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-11

.;D;.;D

REVEL

Pathogenic

0.96

Sift

Pathogenic

0.0

.;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

1.0

MutPred

0.79

Gain of disorder (P = 0.0191);.;Gain of disorder (P = 0.0191);Gain of disorder (P = 0.0191);

MVP

0.96

MPC

1.1

ClinPred

1.0

GERP RS

6.0

Varity_R

0.97

gMVP

0.97

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over