rs2288073

Variant names:

• chr2-24190429-A-G
• rs2288073
• NM_001040710.3:c.419A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040710.3(FAM228A):​c.419A>G​(p.Tyr140Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,612,508 control chromosomes in the GnomAD database, including 70,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5069 hom., cov: 32)
  • Exomes 𝑓: 0.29 (65738 hom.)
• Consequence: FAM228A NM_001040710.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 39 publications found

Genes affected

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

ENSG00000276087 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004767984).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM228A	NM_001040710.3	MANE Select	c.419A>G	p.Tyr140Cys	missense	Exon 6 of 6	NP_001035800.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM228A	ENST00000295150.8	TSL:1 MANE Select	c.419A>G	p.Tyr140Cys	missense	Exon 6 of 6	ENSP00000295150.3
	ENSG00000276087	ENST00000610442.1	TSL:2	n.*1546A>G		non_coding_transcript_exon	Exon 14 of 14	ENSP00000483650.1
	ENSG00000276087	ENST00000610442.1	TSL:2	n.*1546A>G		3_prime_UTR	Exon 14 of 14	ENSP00000483650.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37245 AN: 152044 Hom.: 5064 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.256 AC: 63488 AN: 247650 AF XY: 0.266

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.191

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.295 AC: 430630 AN: 1460346 Hom.: 65738 Cov.: 34 AF XY: 0.296 AC XY: 214994 AN XY: 726506

African (AFR) AF: 0.165 AC: 5500 AN: 33290

American (AMR) AF: 0.124 AC: 5523 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7118 AN: 26088

East Asian (EAS) AF: 0.144 AC: 5725 AN: 39686

South Asian (SAS) AF: 0.304 AC: 26144 AN: 85992

European-Finnish (FIN) AF: 0.274 AC: 14647 AN: 53396

Middle Eastern (MID) AF: 0.224 AC: 1287 AN: 5758

European-Non Finnish (NFE) AF: 0.313 AC: 347714 AN: 1111434

Other (OTH) AF: 0.282 AC: 16972 AN: 60282

GnomAD4 genome AF: 0.245 AC: 37260 AN: 152162 Hom.: 5069 Cov.: 32 AF XY: 0.244 AC XY: 18179 AN XY: 74400

African (AFR) AF: 0.166 AC: 6894 AN: 41514

American (AMR) AF: 0.177 AC: 2701 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3470

East Asian (EAS) AF: 0.178 AC: 921 AN: 5182

South Asian (SAS) AF: 0.311 AC: 1501 AN: 4824

European-Finnish (FIN) AF: 0.281 AC: 2973 AN: 10580

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20538 AN: 67992

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.280 Hom.: 29176

Bravo AF: 0.233

TwinsUK AF: 0.309 AC: 1145

ALSPAC AF: 0.316 AC: 1216

ESP6500AA AF: 0.163 AC: 607

ESP6500EA AF: 0.291 AC: 2376

ExAC AF: 0.259 AC: 31313

Asia WGS AF: 0.217 AC: 758 AN: 3478

EpiCase AF: 0.298

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.31
DANN	Benign	0.53
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.66
PrimateAI	Benign	0.27	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.062
Sift	Benign	0.83	T
Sift4G	Benign	0.087	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.064
ClinPred		0.00016	T
GERP RS		-1.3
Varity_R		0.032
gMVP		0.0048
Mutation Taster		=100/0	polymorphism (auto)

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: rs2288073; hg19: chr2-24413298; COSMIC: COSV54596057;