Variant 15-49541769-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152647.3(FAM227B):c.785C>T(p.Thr262Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,535,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

FAM227B
NM_152647.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

Variant links:

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FAM227B links:

LOC105370811 (HGNC:):

LOC105370811 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
FAM227B	NM_152647.3 linkuse as main transcript	c.785C>T	p.Thr262Met	missense_variant	10/16	ENST00000299338.11
LOC105370811	XR_001751537.2 linkuse as main transcript	n.88+3308G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM227B	ENST00000299338.11 linkuse as main transcript	c.785C>T	p.Thr262Met	missense_variant	10/16	2	NM_152647.3	P1	Q96M60-1
FAM227B	ENST00000561064.5 linkuse as main transcript	c.683C>T	p.Thr228Met	missense_variant	9/11	1			Q96M60-2

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00143

GnomAD3 exomes

AF:

0.0000187

AC:

AN:

214222

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

116986

show subpopulations

Gnomad AFR exome

AF:

0.000151

Gnomad AMR exome

AF:

0.0000388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000411

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000723

AC:

AN:

1383846

Hom.:

Cov.:

AF XY:

0.00000583

AC XY:

AN XY:

686200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000545

Gnomad4 ASJ exome

AF:

0.0000409

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000373

Gnomad4 OTH exome

AF:

0.0000352

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000458

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:

0.00143

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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

Dec 08, 2023

The c.785C>T (p.T262M) alteration is located in exon 10 (coding exon 9) of the FAM227B gene. This alteration results from a C to T substitution at nucleotide position 785, causing the threonine (T) at amino acid position 262 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.24

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.50

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.74

MVP

0.18

MPC

0.27

ClinPred

0.62

GERP RS

3.5

Varity_R

0.15

gMVP

0.46

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