rs1028758884

Variant names:

• chr22-38620244-G-T
• rs1028758884
• NM_001013647.2:c.1006C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-38620244-G-T
• chr22-38620244-G-C

Variant summary

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

The NM_001013647.2(FAM227A):​c.1006C>A​(p.Pro336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,551,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: FAM227A NM_001013647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.61
• Publications: 0 publications found

Genes affected

FAM227A (HGNC:44197): (family with sequence similarity 227 member A)

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=0.04354769).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013647.2. 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
	FAM227A	NM_001013647.2	MANE Select	c.1006C>A	p.Pro336Thr	missense	Exon 11 of 17	NP_001013669.1	F5H4B4-1
	FAM227A	NM_001384270.1		c.739C>A	p.Pro247Thr	missense	Exon 11 of 17	NP_001371199.1
	FAM227A	NM_001291030.2		c.727C>A	p.Pro243Thr	missense	Exon 11 of 17	NP_001277959.1	F5H4B4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227A	ENST00000535113.7	TSL:5 MANE Select	c.1006C>A	p.Pro336Thr	missense	Exon 11 of 17	ENSP00000445093.1	F5H4B4-1
	FAM227A	ENST00000355830.11	TSL:5	c.1006C>A	p.Pro336Thr	missense	Exon 11 of 19	ENSP00000348086.7	A0A0A0MRD0
	FAM227A	ENST00000540952.6	TSL:5	c.1006C>A	p.Pro336Thr	missense	Exon 11 of 17	ENSP00000493504.1	A0A2R8YCE3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.0000447 AC: 7 AN: 156652 AF XY: 0.0000603

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000330

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.0000343 AC: 48 AN: 1399084 Hom.: 0 Cov.: 30 AF XY: 0.0000406 AC XY: 28 AN XY: 690058

African (AFR) AF: 0.0000317 AC: 1 AN: 31590

American (AMR) AF: 0.000140 AC: 5 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49308

Middle Eastern (MID) AF: 0.000356 AC: 2 AN: 5614

European-Non Finnish (NFE) AF: 0.0000306 AC: 33 AN: 1078764

Other (OTH) AF: 0.000121 AC: 7 AN: 57990

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00239 AC: 5 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000113

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	Benign	0.075
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0080
DANN	Benign	0.15
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-2.6
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.011
Sift	Benign	0.59	T
Sift4G	Benign	0.64	T
Polyphen		0.10	B
Vest4		0.058
MutPred		0.21		Loss of loop (P = 0.0288)
MVP		0.014
ClinPred		0.034	T
GERP RS		-6.0
Varity_R		0.024
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1028758884; hg19: chr22-39016249;