Variant chr9-133579044-C-T 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_001080515.3(FAM163B):c.479G>A(p.Arg160His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,561,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FAM163B
NM_001080515.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

FAM163B (HGNC:33277): (family with sequence similarity 163 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM163B links:

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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=0.15440863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM163B	NM_001080515.3 linkuse as main transcript	c.479G>A	p.Arg160His	missense_variant	3/3	ENST00000673969.1	NP_001073984.1	P0C2L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM163B	ENST00000673969.1 linkuse as main transcript	c.479G>A	p.Arg160His	missense_variant	3/3		NM_001080515.3	ENSP00000501259.1		P0C2L3
FAM163B	ENST00000496132.2 linkuse as main transcript	c.479G>A	p.Arg160His	missense_variant	3/3	3		ENSP00000419867.1		P0C2L3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000395

AC:

AN:

75932

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

40466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000120

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000163

AC:

AN:

1408840

Hom.:

Cov.:

AF XY:

0.0000187

AC XY:

AN XY:

696422

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.0000528

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.0000214

Gnomad4 NFE exome

AF:

0.0000129

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

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 08, 2024

The c.479G>A (p.R160H) alteration is located in exon 2 (coding exon 2) of the FAM163B gene. This alteration results from a G to A substitution at nucleotide position 479, causing the arginine (R) at amino acid position 160 to be replaced by a histidine (H). 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

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.13

Sift

Benign

0.078

T;T

Sift4G

Benign

0.085

T;T

Polyphen

0.62

P;P

Vest4

0.14

MVP

0.072

MPC

2.2

ClinPred

0.48

GERP RS

4.1

Varity_R

0.13

gMVP

0.66

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