chr22-38586190-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/17 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

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
FAM227A (HGNC:44197): (family with sequence similarity 227 member A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046086133).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM227ANM_001013647.2 linkc.1648G>A p.Gly550Arg missense_variant Exon 17 of 17 ENST00000535113.7 NP_001013669.1 F5H4B4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM227AENST00000535113.7 linkc.1648G>A p.Gly550Arg missense_variant Exon 17 of 17 5 NM_001013647.2 ENSP00000445093.1 F5H4B4-1
FAM227AENST00000355830.11 linkc.1722G>A p.Lys574Lys synonymous_variant Exon 17 of 19 5 ENSP00000348086.7 A0A0A0MRD0
FAM227AENST00000540952.6 linkc.1722G>A p.Lys574Lys synonymous_variant Exon 17 of 17 5 ENSP00000493504.1 A0A2R8YCE3
FAM227AENST00000543828.1 linkn.-45G>A upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1648G>A (p.G550R) alteration is located in exon 17 (coding exon 16) of the FAM227A gene. This alteration results from a G to A substitution at nucleotide position 1648, causing the glycine (G) at amino acid position 550 to be replaced by an arginine (R). 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
0.12
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
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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs936296330; hg19: chr22-38982195; API