10-118335154-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022063.3(FAM204A):ā€‹c.413A>Gā€‹(p.Asp138Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

FAM204A
NM_022063.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
Variant links:
Genes affected
FAM204A (HGNC:25794): (family with sequence similarity 204 member A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1467557).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM204ANM_022063.3 linkuse as main transcriptc.413A>G p.Asp138Gly missense_variant 6/9 ENST00000369183.9 NP_071346.1 Q9H8W3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM204AENST00000369183.9 linkuse as main transcriptc.413A>G p.Asp138Gly missense_variant 6/91 NM_022063.3 ENSP00000358183.4 Q9H8W3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250850
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135598
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000657
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461192
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726896
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:
0.0000813
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 18, 2024The c.413A>G (p.D138G) alteration is located in exon 6 (coding exon 4) of the FAM204A gene. This alteration results from a A to G substitution at nucleotide position 413, causing the aspartic acid (D) at amino acid position 138 to be replaced by a glycine (G). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.38
T;T;.
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.055
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
.;D;D
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.7
M;M;.
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-5.1
D;D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.046
D;D;T
Polyphen
0.069
B;B;.
Vest4
0.70
MutPred
0.26
Gain of MoRF binding (P = 0.0331);Gain of MoRF binding (P = 0.0331);Gain of MoRF binding (P = 0.0331);
MVP
0.21
MPC
0.31
ClinPred
0.38
T
GERP RS
3.9
Varity_R
0.52
gMVP
0.38

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: rs773380867; hg19: chr10-120094666; API