NM_199136.5:c.73G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_199136.5(FAM221A):​c.73G>A​(p.Gly25Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FAM221A
NM_199136.5 missense

Scores

10
4
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.62
Variant links:
Genes affected
FAM221A (HGNC:27977): (family with sequence similarity 221 member A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.847

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM221ANM_199136.5 linkc.73G>A p.Gly25Ser missense_variant Exon 2 of 7 ENST00000344962.9 NP_954587.2 A4D161-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM221AENST00000344962.9 linkc.73G>A p.Gly25Ser missense_variant Exon 2 of 7 1 NM_199136.5 ENSP00000342576.4 A4D161-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.73G>A (p.G25S) alteration is located in exon 2 (coding exon 2) of the FAM221A gene. This alteration results from a G to A substitution at nucleotide position 73, causing the glycine (G) at amino acid position 25 to be replaced by a serine (S). 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
0.34
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.076
.;T
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Pathogenic
3.1
M;M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Pathogenic
0.73
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.012
D;D
Polyphen
1.0
D;D
Vest4
0.97
MutPred
0.38
Gain of phosphorylation at G25 (P = 0.023);Gain of phosphorylation at G25 (P = 0.023);
MVP
0.39
MPC
0.43
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.73
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.49
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.49
Position offset: -7

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: chr7-23724125; API