4-38905561-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138389.4(FAM114A1):​c.476C>T​(p.Thr159Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000669 in 1,614,104 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 2 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

FAM114A1
NM_138389.4 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.94
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.025874436).
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM114A1NM_138389.4 linkc.476C>T p.Thr159Ile missense_variant Exon 5 of 15 ENST00000358869.5 NP_612398.2 Q8IWE2-1A1MMZ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM114A1ENST00000358869.5 linkc.476C>T p.Thr159Ile missense_variant Exon 5 of 15 1 NM_138389.4 ENSP00000351740.2 Q8IWE2-1
FAM114A1ENST00000515037 linkc.-146C>T 5_prime_UTR_variant Exon 3 of 13 2 ENSP00000424115.1 Q8IWE2-2

Frequencies

GnomAD3 genomes
AF:
0.000374
AC:
57
AN:
152222
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.0614
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
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251394
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135860
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.0000330
AC XY:
24
AN XY:
727244
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:
0.0000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000374
AC:
57
AN:
152222
Hom.:
2
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74362
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
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.000536
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.476C>T (p.T159I) alteration is located in exon 5 (coding exon 3) of the FAM114A1 gene. This alteration results from a C to T substitution at nucleotide position 476, causing the threonine (T) at amino acid position 159 to be replaced by an isoleucine (I). 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
0.43
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.28
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.010
D
Polyphen
0.97
D
Vest4
0.64
MVP
0.79
MPC
0.24
ClinPred
0.69
D
GERP RS
5.5
Varity_R
0.19
gMVP
0.62

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: rs375301582; hg19: chr4-38907182; API