10-115315665-G-C

Position:

• chr10-115315665-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207303.4(ATRNL1):​c.2966G>C​(p.Ser989Thr) 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. 15/21 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 Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ATRNL1 NM_207303.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049871624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRNL1	NM_207303.4	c.2966G>C	p.Ser989Thr	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>C	p.Ser989Thr	missense_variant	18/29	1	NM_207303.4	ENSP00000347152.3
ATRNL1	ENST00000526373.1	c.353G>C	p.Ser118Thr	missense_variant	3/6	5		ENSP00000434118.1
ATRNL1	ENST00000534530.5	n.219G>C		non_coding_transcript_exon_variant	2/6	4
ATRNL1	ENST00000650603.1	n.2858G>C		non_coding_transcript_exon_variant	18/30			ENSP00000497485.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.4
DANN	Benign	0.54
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.49	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.037
Sift	Benign	0.52	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.51		Gain of catalytic residue at S989 (P = 0.0608);
MVP		0.23
MPC		0.20
ClinPred		0.025	T
GERP RS		-2.5
Varity_R		0.050
gMVP		0.22

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;