2-24183552-G-A

Variant names:

• chr2-24183552-G-A
• NM_001040710.3:c.308G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040710.3(FAM228A):​c.308G>A​(p.Ser103Asn) 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. 15/21 in silico tools predict 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: -1.67

Genes affected

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

ENSG00000276087 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10244003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM228A	NM_001040710.3	c.308G>A	p.Ser103Asn	missense_variant	Exon 5 of 6	ENST00000295150.8	NP_001035800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM228A	ENST00000295150.8	c.308G>A	p.Ser103Asn	missense_variant	Exon 5 of 6	1	NM_001040710.3	ENSP00000295150.3
ENSG00000276087	ENST00000610442.1	n.*1435G>A		non_coding_transcript_exon_variant	Exon 13 of 14	2		ENSP00000483650.1
ENSG00000276087	ENST00000610442.1	n.*1435G>A		3_prime_UTR_variant	Exon 13 of 14	2		ENSP00000483650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.308G>A (p.S103N) alteration is located in exon 5 (coding exon 4) of the FAM228A gene. This alteration results from a G to A substitution at nucleotide position 308, causing the serine (S) at amino acid position 103 to be replaced by an asparagine (N). 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	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.35
DANN	Benign	0.92
DEOGEN2	Benign	0.0091	T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.61	N;N
REVEL	Benign	0.083
Sift	Benign	0.19	T;T
Sift4G	Benign	0.080	T;T
Polyphen		0.95	P;.
Vest4		0.23
MutPred		0.26		Gain of catalytic residue at S103 (P = 0.0075);.;
MVP		0.040
MPC		0.053
ClinPred		0.43	T
GERP RS		-4.2
Varity_R		0.038
gMVP		0.0030

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-24406421;