Variant 6-118960168-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_024581.6(FAM184A):c.3358G>A(p.Ala1120Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000281 in 1,461,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

FAM184A
NM_024581.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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:

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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=0.08162016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM184A	NM_024581.6 linkuse as main transcript	c.3358G>A	p.Ala1120Thr	missense_variant	18/18	ENST00000338891.12	NP_078857.5
LOC124901389	XR_007059729.1 linkuse as main transcript	n.76+25178C>T		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3 linkuse as main transcript	c.2851G>A	p.Ala951Thr	missense_variant	17/17		NP_001093881.1
FAM184A	NM_001288576.2 linkuse as main transcript	c.2746G>A	p.Ala916Thr	missense_variant	16/16		NP_001275505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184A	ENST00000338891.12 linkuse as main transcript	c.3358G>A	p.Ala1120Thr	missense_variant	18/18	1	NM_024581.6	ENSP00000342604	P1	Q8NB25-1
	ENST00000518570.2 linkuse as main transcript	n.221+25178C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000811

AC:

AN:

246660

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134028

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1461048

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000911

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.3358G>A (p.A1120T) alteration is located in exon 18 (coding exon 18) of the FAM184A gene. This alteration results from a G to A substitution at nucleotide position 3358, causing the alanine (A) at amino acid position 1120 to be replaced by a threonine (T). 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

-0.41

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0076

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

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D;D;T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.082

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.35

.;.;N;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.24

N;.;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.15

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

Sift4G

Benign

0.22

T;T;T;T;T;T;T

Polyphen

0.17, 0.14

.;.;B;.;.;.;B

Vest4

0.12, 0.13, 0.12, 0.21

MutPred

0.053

.;.;Gain of phosphorylation at A1120 (P = 0.0084);.;.;.;.;

MVP

0.66

MPC

0.18

ClinPred

0.10

GERP RS

5.4

Varity_R

0.12

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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