Variant 6-118961863-C-T 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.3239G>A(p.Arg1080His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FAM184A
NM_024581.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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:

ENSG00000253194 (HGNC:):

ENSG00000253194 links:

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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	Protein	UniProt
FAM184A	NM_024581.6 link	c.3239G>A	p.Arg1080His	missense_variant	17/18	ENST00000338891.12	NP_078857.5	Q8NB25-1Q6P9G8
FAM184A	NM_001100411.3 link	c.2732G>A	p.Arg911His	missense_variant	16/17		NP_001093881.1	Q8NB25-4
FAM184A	NM_001288576.2 link	c.2627G>A	p.Arg876His	missense_variant	15/16		NP_001275505.1	Q8NB25H7BY63Q6P9G8
LOC124901389	XR_007059729.1 link	n.76+26873C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184A	ENST00000338891.12 link	c.3239G>A	p.Arg1080His	missense_variant	17/18	1	NM_024581.6	ENSP00000342604.7		Q8NB25-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

249384

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000662

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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 18, 2023

The c.3239G>A (p.R1080H) alteration is located in exon 17 (coding exon 17) of the FAM184A gene. This alteration results from a G to A substitution at nucleotide position 3239, causing the arginine (R) at amino acid position 1080 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

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.084

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

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.52

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

MetaSVM

Uncertain

0.080

MutationAssessor

Benign

2.0

.;.;M;.;.;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.7

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

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

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

Vest4

0.63, 0.61, 0.70, 0.81, 0.81, 0.71

MutPred

0.17

.;.;Loss of methylation at R1080 (P = 0.0969);.;.;.;.;

MVP

0.83

MPC

0.68

ClinPred

0.76

GERP RS

5.4

Varity_R

0.63

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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