10-115171112-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_207303.4(ATRNL1):c.1168A>G(p.Ile390Val) variant causes a missense change. The variant allele was found at a frequency of 0.0011 in 1,603,620 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (4 hom.)
• Consequence: ATRNL1 NM_207303.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.87

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048526525).
• BP6: Variant 10-115171112-A-G is Benign according to our data. Variant chr10-115171112-A-G is described in ClinVar as [Benign]. Clinvar id is 710446.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRNL1	NM_207303.4	c.1168A>G	p.Ile390Val	missense_variant	8/29	ENST00000355044.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRNL1	ENST00000355044.8	c.1168A>G	p.Ile390Val	missense_variant	8/29	1	NM_207303.4	P1
	ENST00000648967.1	n.818-41999T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000947 AC: 144 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000898

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00137 AC: 341 AN: 248476 Hom.: 0 AF XY: 0.00156 AC XY: 209 AN XY: 134380

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000324

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00287

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000971

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00112 AC: 1625 AN: 1451440 Hom.: 4 Cov.: 30 AF XY: 0.00124 AC XY: 898 AN XY: 721994

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000272

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.00291

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000825

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.000946 AC: 144 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000928 AC XY: 69 AN XY: 74388

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000898

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.000979

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.000868 AC: 3 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	16
Dann	Benign	0.96
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.87	L;L
MutationTaster	Benign	0.93	N
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.19	T;T
Polyphen		0.0010	B;B
Vest4		0.23
MVP		0.093
MPC		0.19
ClinPred		0.020	T
GERP RS		4.7
Varity_R		0.047
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs141967868; hg19: chr10-116930870;