rs751490022

Variant names:

• chr9-35106364-C-G
• rs751490022
• NM_025182.4:c.1106G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-35106364-C-G
• chr9-35106364-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_025182.4(ATOSB):​c.1106G>C​(p.Gly369Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G369D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATOSB NM_025182.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• Publications: 0 publications found

Genes affected

ATOSB (HGNC:25666): (atos homolog B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOSB	NM_025182.4	MANE Select	c.1106G>C	p.Gly369Ala	missense	Exon 6 of 9	NP_079458.2
	ATOSB	NM_001317991.2		c.1106G>C	p.Gly369Ala	missense	Exon 6 of 9	NP_001304920.1	Q7L5A3-1
	ATOSB	NR_134455.2		n.958G>C		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOSB	ENST00000322813.10	TSL:1 MANE Select	c.1106G>C	p.Gly369Ala	missense	Exon 6 of 9	ENSP00000319897.5	Q7L5A3-1
	ATOSB	ENST00000378557.1	TSL:1	c.1106G>C	p.Gly369Ala	missense	Exon 6 of 9	ENSP00000367819.1	Q7L5A3-1
	ATOSB	ENST00000378561.5	TSL:1	c.1106G>C	p.Gly369Ala	missense	Exon 5 of 8	ENSP00000367823.1	Q7L5A3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.78		Loss of sheet (P = 0.0228)
MVP		0.37
MPC		0.86
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.72
gMVP		0.70
Mutation Taster		=8/92	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs751490022; hg19: chr9-35106361;