9-35105757-A-G

Variant names:

• chr9-35105757-A-G
• rs1829957941
• NM_025182.4:c.1388T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025182.4(ATOSB):​c.1388T>C​(p.Leu463Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 152,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ATOSB NM_025182.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOSB	NM_025182.4	c.1388T>C	p.Leu463Pro	missense_variant	Exon 8 of 9	ENST00000322813.10	NP_079458.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOSB	ENST00000322813.10	c.1388T>C	p.Leu463Pro	missense_variant	Exon 8 of 9	1	NM_025182.4	ENSP00000319897.5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74256

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1388T>C (p.L463P) alteration is located in exon 8 (coding exon 6) of the FAM214B gene. This alteration results from a T to C substitution at nucleotide position 1388, causing the leucine (L) at amino acid position 463 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.043	.;T;T;T;T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;.;.;.;.;.;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.74	D;D;D;D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.55	.;N;N;N;N;N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N;.;.;N;.;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.032	D;.;.;D;.;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;D;D;D;D
Vest4		0.88
MutPred		0.44		.;Loss of stability (P = 0.0016);Loss of stability (P = 0.0016);Loss of stability (P = 0.0016);Loss of stability (P = 0.0016);Loss of stability (P = 0.0016);Loss of stability (P = 0.0016);
MVP		0.23
MPC		1.1
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.84

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: rs1829957941; hg19: chr9-35105754;