6-118961780-C-G

Position:

• chr6-118961780-C-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.3322G>C​(p.Gly1108Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,586 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: 0.0000014 (0 hom.)
• Consequence: FAM184A NM_024581.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66

Genes affected

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

ENSG00000253194 (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=0.16870672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM184A	NM_024581.6	c.3322G>C	p.Gly1108Arg	missense_variant	17/18	ENST00000338891.12	NP_078857.5
FAM184A	NM_001100411.3	c.2815G>C	p.Gly939Arg	missense_variant	16/17		NP_001093881.1
FAM184A	NM_001288576.2	c.2710G>C	p.Gly904Arg	missense_variant	15/16		NP_001275505.1
LOC124901389	XR_007059729.1	n.76+26790C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184A	ENST00000338891.12	c.3322G>C	p.Gly1108Arg	missense_variant	17/18	1	NM_024581.6	ENSP00000342604.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727112

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 09, 2024

The c.3322G>C (p.G1108R) alteration is located in exon 17 (coding exon 17) of the FAM184A gene. This alteration results from a G to C substitution at nucleotide position 3322, causing the glycine (G) at amino acid position 1108 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	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T;T;T;.;.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.019
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	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
MutationAssessor	Benign	0.0	.;.;N;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.18	N;.;N;N;.;N;N
REVEL	Benign	0.072
Sift	Benign	0.087	T;.;D;T;.;T;T
Sift4G	Uncertain	0.042	D;D;D;D;T;D;D
Polyphen		0.029, 0.0	.;.;B;.;.;.;B
Vest4		0.24, 0.23, 0.28, 0.29, 0.36, 0.27
MutPred		0.091		.;.;Loss of glycosylation at K1107 (P = 0.0876);.;.;.;.;
MVP		0.39
MPC		0.19
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.14
gMVP		0.079

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-119282945;