Variant 6-118974540-T-C 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_024581.6(FAM184A):c.2803A>G(p.Lys935Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000932 in 1,608,960 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

FAM184A
NM_024581.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

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 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=0.054677755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM184A	NM_024581.6 linkuse as main transcript	c.2803A>G	p.Lys935Glu	missense_variant	14/18	ENST00000338891.12
LOC124901389	XR_007059729.1 linkuse as main transcript	n.76+39550T>C		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3 linkuse as main transcript	c.2408+484A>G		intron_variant
FAM184A	NM_001288576.2 linkuse as main transcript	c.2408+484A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184A	ENST00000338891.12 linkuse as main transcript	c.2803A>G	p.Lys935Glu	missense_variant	14/18	1	NM_024581.6	P1	Q8NB25-1
	ENST00000518570.2 linkuse as main transcript	n.222-31943T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1456780

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000828

AC:

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 03, 2024

The c.2803A>G (p.K935E) alteration is located in exon 14 (coding exon 14) of the FAM184A gene. This alteration results from a A to G substitution at nucleotide position 2803, causing the lysine (K) at amino acid position 935 to be replaced by a glutamic acid (E). 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

Benign

-0.16

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.027

T;T;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.1

N;.;N;.

REVEL

Benign

0.055

Sift

Benign

0.31

T;.;T;.

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.021

.;.;B;.

Vest4

0.40, 0.40, 0.38

MutPred

0.24

.;.;Loss of ubiquitination at K935 (P = 0.0067);.;

MVP

0.12

MPC

0.21

ClinPred

0.36

GERP RS

5.3

Varity_R

0.16

gMVP

0.18

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