chr6-118980164-C-G

Position:

• chr6-118980164-C-G

Variant summary

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

The NM_024581.6(FAM184A):​c.2275G>C​(p.Glu759Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM184A NM_024581.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.40

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 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	c.2275G>C	p.Glu759Gln	missense_variant	10/18	ENST00000338891.12	NP_078857.5
FAM184A	NM_001100411.3	c.1915G>C	p.Glu639Gln	missense_variant	10/17		NP_001093881.1
FAM184A	NM_001288576.2	c.1915G>C	p.Glu639Gln	missense_variant	10/16		NP_001275505.1
LOC124901389	XR_007059729.1	n.76+45174C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184A	ENST00000338891.12	c.2275G>C	p.Glu759Gln	missense_variant	10/18	1	NM_024581.6	ENSP00000342604.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 19, 2024

The c.2275G>C (p.E759Q) alteration is located in exon 10 (coding exon 10) of the FAM184A gene. This alteration results from a G to C substitution at nucleotide position 2275, causing the glutamic acid (E) at amino acid position 759 to be replaced by a glutamine (Q). 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	-0.0057	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T;.;T;.
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;.;.;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	.;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.072	.;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T
Polyphen		1.0	.;D;.;.;D
Vest4		0.62
MutPred		0.056		.;Gain of MoRF binding (P = 0.0669);.;.;Gain of MoRF binding (P = 0.0669);
MVP		0.65
MPC		0.60
ClinPred		0.93	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.12

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: chr6-119301329;