Variant 17-28758709-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077498.3(FAM222B):c.1250C>T(p.Ala417Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000909 in 1,595,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

FAM222B
NM_001077498.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM222B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13551146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM222B	NM_001077498.3 linkuse as main transcript	c.1250C>T	p.Ala417Val	missense_variant	3/3	ENST00000581407.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM222B	ENST00000581407.6 linkuse as main transcript	c.1250C>T	p.Ala417Val	missense_variant	3/3	1	NM_001077498.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

221582

Hom.:

AF XY:

0.0000993

AC XY:

AN XY:

120796

show subpopulations

Gnomad AFR exome

AF:

0.0000778

Gnomad AMR exome

AF:

0.0000322

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000921

AC:

133

AN:

1443390

Hom.:

Cov.:

AF XY:

0.0000895

AC XY:

AN XY:

715420

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

Gnomad4 AMR exome

AF:

0.0000948

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000965

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000580

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.1250C>T (p.A417V) alteration is located in exon 4 (coding exon 2) of the FAM222B gene. This alteration results from a C to T substitution at nucleotide position 1250, causing the alanine (A) at amino acid position 417 to be replaced by a valine (V). 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

Benign

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

D;.;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.61

D;D;D;D

PrimateAI

Uncertain

0.67

REVEL

Benign

0.065

Sift4G

Uncertain

0.053

T;D;D

Polyphen

0.66

.;P;P

Vest4

0.24

MutPred

0.30

.;Gain of catalytic residue at A417 (P = 0.0499);Gain of catalytic residue at A417 (P = 0.0499);

MVP

0.043

MPC

0.14

ClinPred

0.044

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over