6-118975940-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024581.6(FAM184A):c.2560A>C(p.Ser854Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,842 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FAM184A NM_024581.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

Genes affected

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

(HGNC:):

ACMG classification

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=0.16507438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM184A	NM_024581.6	c.2560A>C	p.Ser854Arg	missense_variant	12/18	ENST00000338891.12
LOC124901389	XR_007059729.1	n.76+40950T>G		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3	c.2200A>C	p.Ser734Arg	missense_variant	12/17
FAM184A	NM_001288576.2	c.2200A>C	p.Ser734Arg	missense_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184A	ENST00000338891.12	c.2560A>C	p.Ser854Arg	missense_variant	12/18	1	NM_024581.6	P1
	ENST00000518570.2	n.222-30543T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460842 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.2560A>C (p.S854R) alteration is located in exon 12 (coding exon 12) of the FAM184A gene. This alteration results from a A to C substitution at nucleotide position 2560, causing the serine (S) at amino acid position 854 to be replaced by an arginine (R). 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	-0.070	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T;.;.;T;.
Eigen	Benign	0.098
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.68	D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N;.;N;N;.;N;N
REVEL	Benign	0.069
Sift	Benign	0.030	D;.;D;D;.;D;D
Sift4G	Uncertain	0.055	T;T;T;T;T;T;T
Polyphen		0.51, 0.63	.;.;P;.;.;.;P
Vest4		0.50, 0.49, 0.54, 0.43, 0.52, 0.54
MutPred		0.15		.;.;Loss of phosphorylation at S854 (P = 0.0071);.;.;.;Loss of phosphorylation at S854 (P = 0.0071);
MVP		0.37
MPC		0.21
ClinPred		0.86	D
GERP RS		5.2
Varity_R		0.15
gMVP		0.63

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

Other links and lift over

dbSNP: rs1000905754; hg19: chr6-119297105;