12-50330600-C-T

Variant summary

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

The NM_001145475.3(FAM186A):​c.7007G>A​(p.Arg2336Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,398,258 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

FAM186A
NM_001145475.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
FAM186A (HGNC:26980): (family with sequence similarity 186 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=0.17563573).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM186ANM_001145475.3 linkc.7007G>A p.Arg2336Gln missense_variant Exon 7 of 8 ENST00000327337.6 NP_001138947.1 A6NE01

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM186AENST00000327337.6 linkc.7007G>A p.Arg2336Gln missense_variant Exon 7 of 8 5 NM_001145475.3 ENSP00000329995.5 A6NE01

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000265
AC:
37
AN:
1398258
Hom.:
0
Cov.:
31
AF XY:
0.0000290
AC XY:
20
AN XY:
689570
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000281
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:
0.0000325
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000756

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.7007G>A (p.R2336Q) alteration is located in exon 7 (coding exon 7) of the FAM186A gene. This alteration results from a G to A substitution at nucleotide position 7007, causing the arginine (R) at amino acid position 2336 to be replaced by a glutamine (Q). 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
0.14
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0074
.;.;T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.83
T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;.;M
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.5
D;N;N
REVEL
Benign
0.079
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.26
T;T;T
Polyphen
1.0
.;D;D
Vest4
0.28
MVP
0.076
ClinPred
0.89
D
GERP RS
3.3
Varity_R
0.069
gMVP
0.016

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
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: rs1223115458; hg19: chr12-50724383; API