2-24175563-C-A

Variant names:

• chr2-24175563-C-A
• rs747128968
• NM_001040710.3:c.83C>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.83C>A​(p.Ser28Tyr) 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. 15/22 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. S28C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FAM228A NM_001040710.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 1 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=0.24717546).

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.83C>A	p.Ser28Tyr	missense	Exon 2 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.83C>A	p.Ser28Tyr	missense	Exon 2 of 6	ENSP00000295150.3	Q86W67
	ENSG00000276087	ENST00000610442.1	TSL:2	n.*996C>A		non_coding_transcript_exon	Exon 9 of 14	ENSP00000483650.1	A0A087X0T9
	ENSG00000276087	ENST00000610442.1	TSL:2	n.*996C>A		3_prime_UTR	Exon 9 of 14	ENSP00000483650.1	A0A087X0T9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

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	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Benign	0.0046
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.48
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.46		Loss of disorder (P = 0.0106)
MVP		0.47
MPC		0.12
ClinPred		0.60	D
GERP RS		3.8
PromoterAI		-0.081	Neutral
Varity_R		0.15
gMVP		0.040
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747128968; hg19: chr2-24398432;