10-115160047-T-A

Variant summary

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

The NM_207303.4(ATRNL1):c.837T>A(p.Asp279Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATRNL1 NM_207303.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRNL1	NM_207303.4	c.837T>A	p.Asp279Glu	missense_variant	6/29	ENST00000355044.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRNL1	ENST00000355044.8	c.837T>A	p.Asp279Glu	missense_variant	6/29	1	NM_207303.4	P1
	ENST00000648967.1	n.818-30934A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.837T>A (p.D279E) alteration is located in exon 6 (coding exon 6) of the ATRNL1 gene. This alteration results from a T to A substitution at nucleotide position 837, causing the aspartic acid (D) at amino acid position 279 to be replaced by a glutamic acid (E). 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	0.81
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.9	L;.;.;L
MutationTaster	Benign	0.58	N
PrimateAI	Pathogenic	0.83	D
Sift4G	Uncertain	0.048	D;T;T;D
Polyphen		1.0	D;D;.;D
Vest4		0.84
MutPred		0.59		Gain of loop (P = 0.1069);.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.56
MPC		0.80
ClinPred		0.98	D
GERP RS		2.3
Varity_R		0.37
gMVP		0.59

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: chr10-116919808;