Genetic Variant FAM184B:p.Arg947Gln (chr4-17635058-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_015688.2(FAM184B):c.2840G>A(p.Arg947Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,551,762 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)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FAM184B
NM_015688.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

Variant links:

Genes affected

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

FAM184B 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 rank	MANE	Protein	UniProt
FAM184B	NM_015688.2 link	c.2840G>A	p.Arg947Gln	missense_variant	Exon 16 of 18	ENST00000265018.4	NP_056503.1	Q9ULE4
FAM184B	XM_047450066.1 link	c.2840G>A	p.Arg947Gln	missense_variant	Exon 16 of 17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4 link	c.2840G>A	p.Arg947Gln	missense_variant	Exon 16 of 18	1	NM_015688.2	ENSP00000265018.3		Q9ULE4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

157316

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

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:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1399542

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

690292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000394

AC:

Asia WGS

AF:

0.000577

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

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2840G>A (p.R947Q) alteration is located in exon 16 (coding exon 16) of the FAM184B gene. This alteration results from a G to A substitution at nucleotide position 2840, causing the arginine (R) at amino acid position 947 to be replaced by a glutamine (Q). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

REVEL

Benign

0.16

Sift

Uncertain

0.011

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.61

MutPred

0.20

Gain of glycosylation at S948 (P = 0.013);

MVP

0.13

ClinPred

0.92

GERP RS

6.2

Varity_R

0.29

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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