2-24190473-C-G

Variant names:

• chr2-24190473-C-G
• rs374755608
• NM_001040710.3:c.463C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040710.3(FAM228A):​c.463C>G​(p.Leu155Val) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L155I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM228A NM_001040710.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 0 publications found

Genes affected

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

ENSG00000276087 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028111726).

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.463C>G	p.Leu155Val	missense	Exon 6 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.463C>G	p.Leu155Val	missense	Exon 6 of 6	ENSP00000295150.3	Q86W67
	FAM228A	ENST00000432434.2	TSL:5	c.580C>G	p.Leu194Val	missense	Exon 6 of 7	ENSP00000412833.2	H7C3M9
	FAM228A	ENST00000965618.1		c.394C>G	p.Leu132Val	missense	Exon 5 of 5	ENSP00000635677.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.5
DANN	Benign	0.61
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		-0.080
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.034
Sift	Benign	0.71	T
Sift4G	Benign	0.48	T
Polyphen		0.046	B
Vest4		0.018
MutPred		0.19		Gain of MoRF binding (P = 0.089)
MVP		0.040
MPC		0.084
ClinPred		0.063	T
GERP RS		-0.39
Varity_R		0.080
gMVP		0.0052
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs374755608; hg19: chr2-24413342;