2-24177815-A-G

Variant names:

• chr2-24177815-A-G
• NM_001040710.3:c.107A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040710.3(FAM228A):​c.107A>G​(p.Glu36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM228A NM_001040710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

Genes affected

FAM228A (HGNC:34418): (family with sequence similarity 228 member A)

ENSG00000276087 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3759806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM228A	NM_001040710.3	c.107A>G	p.Glu36Gly	missense_variant	Exon 3 of 6	ENST00000295150.8	NP_001035800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM228A	ENST00000295150.8	c.107A>G	p.Glu36Gly	missense_variant	Exon 3 of 6	1	NM_001040710.3	ENSP00000295150.3
ENSG00000276087	ENST00000610442.1	n.*1234A>G		non_coding_transcript_exon_variant	Exon 11 of 14	2		ENSP00000483650.1
ENSG00000276087	ENST00000610442.1	n.*1234A>G		3_prime_UTR_variant	Exon 11 of 14	2		ENSP00000483650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107A>G (p.E36G) alteration is located in exon 3 (coding exon 2) of the FAM228A gene. This alteration results from a A to G substitution at nucleotide position 107, causing the glutamic acid (E) at amino acid position 36 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.078
Eigen_PC	Benign	0.081
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.39		Gain of loop (P = 0.0045);
MVP		0.66
MPC		0.37
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.36
gMVP		0.055

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-24400684;