Variant 6-118960120-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_024581.6(FAM184A):c.3406C>T(p.Arg1136Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,116 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: 0.000036 ( 0 hom. )

Consequence

FAM184A
NM_024581.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Variant links:

Genes affected

FAM184A (HGNC:20991): (family with sequence similarity 184 member A) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

FAM184A links:

(HGNC:):

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
FAM184A	NM_024581.6 linkuse as main transcript	c.3406C>T	p.Arg1136Trp	missense_variant	18/18	ENST00000338891.12
LOC124901389	XR_007059729.1 linkuse as main transcript	n.76+25130G>A		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3 linkuse as main transcript	c.2899C>T	p.Arg967Trp	missense_variant	17/17
FAM184A	NM_001288576.2 linkuse as main transcript	c.2794C>T	p.Arg932Trp	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184A	ENST00000338891.12 linkuse as main transcript	c.3406C>T	p.Arg1136Trp	missense_variant	18/18	1	NM_024581.6	P1	Q8NB25-1
	ENST00000518570.2 linkuse as main transcript	n.221+25130G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

247096

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

134278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1460968

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jan 07, 2022

The c.3406C>T (p.R1136W) alteration is located in exon 18 (coding exon 18) of the FAM184A gene. This alteration results from a C to T substitution at nucleotide position 3406, causing the arginine (R) at amino acid position 1136 to be replaced by a tryptophan (W). 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

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.18

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.087

T;T;T;.;T;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D

MetaSVM

Benign

-0.68

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.4

D;.;D;N;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;.;.;D

Vest4

0.68, 0.63, 0.29, 0.80

MutPred

0.40

.;.;Loss of disorder (P = 0);.;.;.;.;

MVP

0.80

MPC

0.65

ClinPred

0.83

GERP RS

5.4

Varity_R

0.25

gMVP

0.38

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