10-115129484-T-G

Position:

• chr10-115129484-T-G

Variant summary

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

The NM_207303.4(ATRNL1):​c.778T>G​(p.Tyr260Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATRNL1 NM_207303.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

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]

ENSG00000285582 (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	Protein	UniProt
ATRNL1	NM_207303.4	c.778T>G	p.Tyr260Asp	missense_variant	5/29	ENST00000355044.8	NP_997186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRNL1	ENST00000355044.8	c.778T>G	p.Tyr260Asp	missense_variant	5/29	1	NM_207303.4	ENSP00000347152.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727188

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Sep 02, 2024

The c.778T>G (p.Y260D) alteration is located in exon 5 (coding exon 5) of the ATRNL1 gene. This alteration results from a T to G substitution at nucleotide position 778, causing the tyrosine (Y) at amino acid position 260 to be replaced by an aspartic acid (D). 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	0.93
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	.;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.1	L;.;.;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.2	.;D;.;D
REVEL	Uncertain	0.30
Sift	Benign	0.14	.;T;.;T
Sift4G	Benign	0.068	T;T;T;T
Polyphen		0.94	P;P;.;P
Vest4		0.87
MutPred		0.55		Gain of disorder (P = 0.0062);.;Gain of disorder (P = 0.0062);Gain of disorder (P = 0.0062);
MVP		0.41
MPC		1.1
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.31
gMVP		0.63

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: chr10-116889246;