2-24183565-C-A

Variant names:

• chr2-24183565-C-A
• rs1377062257
• NM_001040710.3:c.321C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

Genes affected

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

ENSG00000276087 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09290865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040710.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM228A	NM_001040710.3	MANE Select	c.321C>A	p.Phe107Leu	missense	Exon 5 of 6	NP_001035800.1	Q86W67

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM228A	ENST00000295150.8	TSL:1 MANE Select	c.321C>A	p.Phe107Leu	missense	Exon 5 of 6	ENSP00000295150.3	Q86W67
	ENSG00000276087	ENST00000610442.1	TSL:2	n.*1448C>A		non_coding_transcript_exon	Exon 13 of 14	ENSP00000483650.1	A0A087X0T9
	ENSG00000276087	ENST00000610442.1	TSL:2	n.*1448C>A		3_prime_UTR	Exon 13 of 14	ENSP00000483650.1	A0A087X0T9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.065
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.011
Sift	Benign	0.056	T
Sift4G	Benign	0.21	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
PromoterAI		-0.15	Neutral
Varity_R		0.060
gMVP		0.0080
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1377062257; hg19: chr2-24406434;