chr5-154027238-C-T

Variant names:

• chr5-154027238-C-T
• rs1771847609
• NM_018691.4:c.727G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018691.4(FAM114A2):​c.727G>A​(p.Glu243Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.73

Genes affected

FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A2	NM_018691.4	c.727G>A	p.Glu243Lys	missense_variant	Exon 7 of 14	ENST00000351797.9	NP_061161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM114A2	ENST00000351797.9	c.727G>A	p.Glu243Lys	missense_variant	Exon 7 of 14	1	NM_018691.4	ENSP00000341597.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.727G>A (p.E243K) alteration is located in exon 7 (coding exon 6) of the FAM114A2 gene. This alteration results from a G to A substitution at nucleotide position 727, causing the glutamic acid (E) at amino acid position 243 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;T;T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.0	M;M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.96
MutPred		0.73		Gain of methylation at E243 (P = 0.0017);Gain of methylation at E243 (P = 0.0017);Gain of methylation at E243 (P = 0.0017);.;
MVP		0.49
MPC		0.19
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.41

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: rs1771847609; hg19: chr5-153406798;