chr22-38586190-C-T

Variant names:

• chr22-38586190-C-T
• rs936296330
• NM_001013647.2:c.1648G>A

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.1648G>A​(p.Gly550Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,551,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM227A NM_001013647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08
• 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=0.046086133).

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.1648G>A	p.Gly550Arg	missense	Exon 17 of 17	NP_001013669.1	F5H4B4-1
	FAM227A	NM_001291030.2		c.1369G>A	p.Gly457Arg	missense	Exon 17 of 17	NP_001277959.1	F5H4B4-2
	FAM227A	NM_001384271.1		c.1084G>A	p.Gly362Arg	missense	Exon 15 of 15	NP_001371200.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227A	ENST00000535113.7	TSL:5 MANE Select	c.1648G>A	p.Gly550Arg	missense	Exon 17 of 17	ENSP00000445093.1	F5H4B4-1
	FAM227A	ENST00000355830.11	TSL:5	c.1722G>A	p.Lys574Lys	synonymous	Exon 17 of 19	ENSP00000348086.7	A0A0A0MRD0
	FAM227A	ENST00000540952.6	TSL:5	c.1722G>A	p.Lys574Lys	synonymous	Exon 17 of 17	ENSP00000493504.1	A0A2R8YCE3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1398954 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690002

African (AFR) AF: 0.00 AC: 0 AN: 31556

American (AMR) AF: 0.00 AC: 0 AN: 35522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 79144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078856

Other (OTH) AF: 0.00 AC: 0 AN: 57988

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2090

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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.1
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.021
Sift	Benign	0.054	T
Sift4G	Benign	0.50	T
Polyphen		0.043	B
Vest4		0.079
MutPred		0.11		Gain of MoRF binding (P = 0.0186)
MVP		0.048
ClinPred		0.050	T
GERP RS		-0.32
Varity_R		0.10
Mutation Taster		=72/28	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: rs936296330; hg19: chr22-38982195;