NM_001013647.2:c.1688T>G

Variant names:

• chr22-38586150-A-C
• NM_001013647.2:c.1688T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013647.2(FAM227A):​c.1688T>G​(p.Phe563Cys) 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. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM227A NM_001013647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.100
• Publications: 0 publications found

Genes affected

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

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=0.09277755).

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.1688T>G	p.Phe563Cys	missense	Exon 17 of 17	NP_001013669.1	F5H4B4-1
	FAM227A	NM_001384270.1		c.1495T>G	p.Ser499Ala	missense	Exon 17 of 17	NP_001371199.1
	FAM227A	NM_001291030.2		c.1409T>G	p.Phe470Cys	missense	Exon 17 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.1688T>G	p.Phe563Cys	missense	Exon 17 of 17	ENSP00000445093.1	F5H4B4-1
	FAM227A	ENST00000355830.11	TSL:5	c.1762T>G	p.Ser588Ala	missense	Exon 17 of 19	ENSP00000348086.7	A0A0A0MRD0
	FAM227A	ENST00000540952.6	TSL:5	c.1762T>G	p.Ser588Ala	missense	Exon 17 of 17	ENSP00000493504.1	A0A2R8YCE3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.087
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.10
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.054
Sift	Uncertain	0.016	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.15
MutPred		0.17		Loss of sheet (P = 0.1158)
MVP		0.048
ClinPred		0.11	T
GERP RS		0.85
Varity_R		0.084
Mutation Taster		=98/2	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

hg19: chr22-38982155;