chr4-186152018-A-G

Position:

• chr4-186152018-A-G

Variant summary

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

The NM_001395294.1(FAM149A):​c.932A>G​(p.Glu311Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM149A NM_001395294.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

Genes affected

FAM149A (HGNC:24527): (family with sequence similarity 149 member A)

FAM149A (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
FAM149A	NM_001395294.1	c.932A>G	p.Glu311Gly	missense_variant	4/14		NP_001382223.1
FAM149A	NM_001367768.3	c.905A>G	p.Glu302Gly	missense_variant	4/14		NP_001354697.1
FAM149A	NM_001006655.3	c.59A>G	p.Glu20Gly	missense_variant	4/14		NP_001006656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM149A	ENST00000706927.1	c.932A>G	p.Glu311Gly	missense_variant	4/14			ENSP00000516649.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Sep 26, 2024

The c.59A>G (p.E20G) alteration is located in exon 4 (coding exon 1) of the FAM149A gene. This alteration results from a A to G substitution at nucleotide position 59, causing the glutamic acid (E) at amino acid position 20 to be replaced by a glycine (G). 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
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	.;T;.;.;.;.;.;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	.;T;D;D;T;.;.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.9	.;M;.;.;.;.;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.2	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.;.;.;.
Vest4		0.61
MutPred		0.30		.;Gain of MoRF binding (P = 0.0514);.;.;.;.;.;.;.;
MVP		0.83
MPC		0.52
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.89
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: 27

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: chr4-187073172;