6-118975948-A-G

Variant summary

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

The NM_024581.6(FAM184A):c.2552T>C(p.Leu851Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 8.06

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM184A	NM_024581.6	c.2552T>C	p.Leu851Ser	missense_variant	12/18	ENST00000338891.12
LOC124901389	XR_007059729.1	n.76+40958A>G		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3	c.2192T>C	p.Leu731Ser	missense_variant	12/17
FAM184A	NM_001288576.2	c.2192T>C	p.Leu731Ser	missense_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184A	ENST00000338891.12	c.2552T>C	p.Leu851Ser	missense_variant	12/18	1	NM_024581.6	P1
	ENST00000518570.2	n.222-30535A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 27, 2022

The c.2552T>C (p.L851S) alteration is located in exon 12 (coding exon 12) of the FAM184A gene. This alteration results from a T to C substitution at nucleotide position 2552, causing the leucine (L) at amino acid position 851 to be replaced by a serine (S). 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	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T;.;.;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D;D;D;D;T;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D;.;D;D;.;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D;.;D;D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;T;D;T;D
Polyphen		1.0	.;.;D;.;.;.;D
Vest4		0.92, 0.93, 0.91, 0.90, 0.89
MutPred		0.28		.;.;Gain of phosphorylation at L851 (P = 0.0252);.;.;.;Gain of phosphorylation at L851 (P = 0.0252);
MVP		0.67
MPC		0.54
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.69
gMVP		0.71

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: rs1783831114; hg19: chr6-119297113;