10-115315665-G-A

Position:

• chr10-115315665-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207303.4(ATRNL1):​c.2966G>A​(p.Ser989Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 1,613,860 control chromosomes in the GnomAD database, including 756,866 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.97 (71335 hom., cov: 30)
  • Exomes 𝑓: 0.97 (685531 hom.)
• Consequence: ATRNL1 NM_207303.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.614

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.1559637E-7).
• BP6: Variant 10-115315665-G-A is Benign according to our data. Variant chr10-115315665-G-A is described in ClinVar as [Benign]. Clinvar id is 1320613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRNL1	NM_207303.4	c.2966G>A	p.Ser989Asn	missense_variant	18/29	ENST00000355044.8	NP_997186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRNL1	ENST00000355044.8	c.2966G>A	p.Ser989Asn	missense_variant	18/29	1	NM_207303.4	ENSP00000347152.3
ATRNL1	ENST00000526373.1	c.353G>A	p.Ser118Asn	missense_variant	3/6	5		ENSP00000434118.1
ATRNL1	ENST00000534530.5	n.219G>A		non_coding_transcript_exon_variant	2/6	4
ATRNL1	ENST00000650603.1	n.2858G>A		non_coding_transcript_exon_variant	18/30			ENSP00000497485.1

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147218 AN: 152070 Hom.: 71279 Cov.: 30

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.967

GnomAD3 exomes AF: 0.974 AC: 244790 AN: 251330 Hom.: 119243 AF XY: 0.974 AC XY: 132253 AN XY: 135828

Gnomad AFR exome AF: 0.954

Gnomad AMR exome AF: 0.984

Gnomad ASJ exome AF: 0.982

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.966

Gnomad FIN exome AF: 0.974

Gnomad NFE exome AF: 0.971

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.968 AC: 1415477 AN: 1461672 Hom.: 685531 Cov.: 55 AF XY: 0.968 AC XY: 704200 AN XY: 727148

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.981

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.965

Gnomad4 FIN exome AF: 0.974

Gnomad4 NFE exome AF: 0.967

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.968 AC: 147333 AN: 152188 Hom.: 71335 Cov.: 30 AF XY: 0.969 AC XY: 72077 AN XY: 74390

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.967

Alfa AF: 0.972 Hom.: 132197

Bravo AF: 0.968

TwinsUK AF: 0.970 AC: 3595

ALSPAC AF: 0.963 AC: 3712

ESP6500AA AF: 0.958 AC: 4219

ESP6500EA AF: 0.968 AC: 8329

ExAC AF: 0.974 AC: 118227

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.49
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.066	T
MetaRNN	Benign	8.2e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.32	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.028
Sift	Benign	0.82	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.026
MPC		0.21
ClinPred		0.00055	T
GERP RS		-2.5
Varity_R		0.043
gMVP		0.16

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: rs1953758; hg19: chr10-117075175;