6-119002978-T-A

Variant summary

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

The NM_024581.6(FAM184A):c.2009A>T(p.Gln670Leu) 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: 33)
• Consequence: FAM184A NM_024581.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

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.2009A>T	p.Gln670Leu	missense_variant	9/18	ENST00000338891.12
LOC124901389	XR_007059729.1	n.77-28427T>A		intron_variant, non_coding_transcript_variant
FAM184A	NM_001100411.3	c.1649A>T	p.Gln550Leu	missense_variant	9/17
FAM184A	NM_001288576.2	c.1649A>T	p.Gln550Leu	missense_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184A	ENST00000338891.12	c.2009A>T	p.Gln670Leu	missense_variant	9/18	1	NM_024581.6	P1
	ENST00000518570.2	n.222-3505T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 01, 2022

The c.2009A>T (p.Q670L) alteration is located in exon 9 (coding exon 9) of the FAM184A gene. This alteration results from a A to T substitution at nucleotide position 2009, causing the glutamine (Q) at amino acid position 670 to be replaced by a leucine (L). 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	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	33
Dann	Uncertain	1.0
DEOGEN2	Benign	0.060	T;T;.;T;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.61	T
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.99, 0.99	.;D;.;.;D
Vest4		0.73
MutPred		0.27		.;Gain of stability (P = 0.0424);.;.;Gain of stability (P = 0.0424);
MVP		0.74
MPC		0.63
ClinPred		0.98	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: -11

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: chr6-119324143;