22-38586150-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/17 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09277755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227A	NM_001013647.2	c.1688T>G	p.Phe563Cys	missense_variant	Exon 17 of 17	ENST00000535113.7	NP_001013669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227A	ENST00000535113.7	c.1688T>G	p.Phe563Cys	missense_variant	Exon 17 of 17	5	NM_001013647.2	ENSP00000445093.1
FAM227A	ENST00000355830.11	c.1762T>G	p.Ser588Ala	missense_variant	Exon 17 of 19	5		ENSP00000348086.7
FAM227A	ENST00000540952.6	c.1762T>G	p.Ser588Ala	missense_variant	Exon 17 of 17	5		ENSP00000493504.1
FAM227A	ENST00000543828.1	n.-5T>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1688T>G (p.F563C) alteration is located in exon 17 (coding exon 16) of the FAM227A gene. This alteration results from a T to G substitution at nucleotide position 1688, causing the phenylalanine (F) at amino acid position 563 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-38982155;