2-24183565-C-A

Position:

• chr2-24183565-C-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.321C>A​(p.Phe107Leu) 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. 12/21 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: -0.0650

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=0.09290865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM228A	NM_001040710.3	c.321C>A	p.Phe107Leu	missense_variant	5/6	ENST00000295150.8	NP_001035800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM228A	ENST00000295150.8	c.321C>A	p.Phe107Leu	missense_variant	5/6	1	NM_001040710.3	ENSP00000295150.3
ENSG00000276087	ENST00000610442.1	n.*1448C>A		non_coding_transcript_exon_variant	13/14	2		ENSP00000483650.1
ENSG00000276087	ENST00000610442.1	n.*1448C>A		3_prime_UTR_variant	13/14	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.321C>A (p.F107L) alteration is located in exon 5 (coding exon 4) of the FAM228A gene. This alteration results from a C to A substitution at nucleotide position 321, causing the phenylalanine (F) at amino acid position 107 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
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.3
DANN	Benign	0.83
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N;D
REVEL	Benign	0.011
Sift	Benign	0.056	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.043	B;.
Vest4		0.25
MutPred		0.32		Loss of sheet (P = 0.0357);.;
MVP		0.030
MPC		0.17
ClinPred		0.13	T
GERP RS		0.98
Varity_R		0.060
gMVP		0.0080

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: chr2-24406434;