chr10-115215756-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_207303.4(ATRNL1):c.1408C>T(p.His470Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,906 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: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ATRNL1
NM_207303.4 missense
NM_207303.4 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 7.19
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]
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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, 0.948
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRNL1 | NM_207303.4 | c.1408C>T | p.His470Tyr | missense_variant | 9/29 | ENST00000355044.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRNL1 | ENST00000355044.8 | c.1408C>T | p.His470Tyr | missense_variant | 9/29 | 1 | NM_207303.4 | P1 | |
ENST00000648967.1 | n.817+214G>A | intron_variant, non_coding_transcript_variant | |||||||
ATRNL1 | ENST00000524503.1 | n.100C>T | non_coding_transcript_exon_variant | 2/3 | 3 | ||||
ATRNL1 | ENST00000650603.1 | c.1300C>T | p.His434Tyr | missense_variant, NMD_transcript_variant | 9/30 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000812 AC: 2AN: 246246Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133282
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1456906Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724706
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 13, 2022 | The c.1408C>T (p.H470Y) alteration is located in exon 9 (coding exon 9) of the ATRNL1 gene. This alteration results from a C to T substitution at nucleotide position 1408, causing the histidine (H) at amino acid position 470 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of phosphorylation at H470 (P = 0.0675);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at