Variant 11-82732583-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_175885.4(FAM181B):c.1147C>T(p.Pro383Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000243 in 1,603,012 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

FAM181B
NM_175885.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

FAM181B (HGNC:28512): (family with sequence similarity 181 member B)

FAM181B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.055107415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM181B	NM_175885.4 linkuse as main transcript	c.1147C>T	p.Pro383Ser	missense_variant	1/1	ENST00000329203.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM181B	ENST00000329203.5 linkuse as main transcript	c.1147C>T	p.Pro383Ser	missense_variant	1/1		NM_175885.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000329

AC:

AN:

218778

Hom.:

AF XY:

0.000380

AC XY:

AN XY:

121122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000485

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000300

Gnomad SAS exome

AF:

0.000695

Gnomad FIN exome

AF:

0.0000509

Gnomad NFE exome

AF:

0.000298

Gnomad OTH exome

AF:

0.000374

GnomAD4 exome

AF:

0.000235

AC:

341

AN:

1450862

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

182

AN XY:

720988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000456

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00125

Gnomad4 SAS exome

AF:

0.000647

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.000168

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.000315

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.000269

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

May 08, 2024

The c.1147C>T (p.P383S) alteration is located in exon 1 (coding exon 1) of the FAM181B gene. This alteration results from a C to T substitution at nucleotide position 1147, causing the proline (P) at amino acid position 383 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

Eigen

Benign

0.039

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.54

M_CAP

Benign

0.015

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.082

Sift

Uncertain

0.016

Sift4G

Benign

0.15

Polyphen

0.46

Vest4

0.27

MVP

0.28

MPC

1.2

ClinPred

0.045

GERP RS

4.2

Varity_R

0.14

gMVP

0.13

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