chr4-38914922-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138389.4(FAM114A1):c.794T>C(p.Met265Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
FAM114A1
NM_138389.4 missense, splice_region
NM_138389.4 missense, splice_region
Scores
5
7
5
Splicing: ADA: 0.8492
2
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
FAM114A1 (HGNC:25087): (family with sequence similarity 114 member A1) The protein encoded by this gene belongs to the FAM114 family and may play a role in neuronal cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAM114A1 | NM_138389.4 | c.794T>C | p.Met265Thr | missense_variant, splice_region_variant | 8/15 | ENST00000358869.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM114A1 | ENST00000358869.5 | c.794T>C | p.Met265Thr | missense_variant, splice_region_variant | 8/15 | 1 | NM_138389.4 | P1 | |
FAM114A1 | ENST00000515037.5 | c.173T>C | p.Met58Thr | missense_variant, splice_region_variant | 6/13 | 2 | |||
FAM114A1 | ENST00000512889.1 | n.304T>C | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251048Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135718
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461496Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727050
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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 submitter | clinical testing | Ambry Genetics | Jan 26, 2023 | The c.794T>C (p.M265T) alteration is located in exon 8 (coding exon 6) of the FAM114A1 gene. This alteration results from a T to C substitution at nucleotide position 794, causing the methionine (M) at amino acid position 265 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.97
.;D
Vest4
MutPred
0.71
.;Gain of glycosylation at S261 (P = 0.0058);
MVP
MPC
0.34
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at