10-115315665-G-T

Variant names:

• chr10-115315665-G-T
• rs1953758
• NM_207303.4:c.2966G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207303.4(ATRNL1):​c.2966G>T​(p.Ser989Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S989N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ATRNL1 NM_207303.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081101954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207303.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRNL1	NM_207303.4	MANE Select	c.2966G>T	p.Ser989Ile	missense	Exon 18 of 29	NP_997186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRNL1	ENST00000355044.8	TSL:1 MANE Select	c.2966G>T	p.Ser989Ile	missense	Exon 18 of 29	ENSP00000347152.3
	ATRNL1	ENST00000526373.1	TSL:5	c.353G>T	p.Ser118Ile	missense	Exon 3 of 6	ENSP00000434118.1
	ATRNL1	ENST00000534530.5	TSL:4	n.219G>T		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.61
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.046
Sift	Benign	0.15	T
Sift4G	Benign	0.16	T
Polyphen		0.025	B
Vest4		0.20
MutPred		0.50		Loss of disorder (P = 0.032)
MVP		0.16
MPC		0.30
ClinPred		0.059	T
GERP RS		-2.5
Varity_R		0.094
gMVP		0.39
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1953758; hg19: chr10-117075175;