12-50350970-T-G

Variant summary

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

The NM_001145475.3(FAM186A):​c.5862A>C​(p.Lys1954Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

FAM186A
NM_001145475.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.450
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=0.16271743).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM186ANM_001145475.3 linkc.5862A>C p.Lys1954Asn missense_variant Exon 4 of 8 ENST00000327337.6 NP_001138947.1 A6NE01

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM186AENST00000327337.6 linkc.5862A>C p.Lys1954Asn missense_variant Exon 4 of 8 5 NM_001145475.3 ENSP00000329995.5 A6NE01
FAM186AENST00000543111.5 linkc.5862A>C p.Lys1954Asn missense_variant Exon 4 of 8 5 ENSP00000441337.1 F5GYN0
FAM186AENST00000543096.5 linkc.-106A>C upstream_gene_variant 2 ENSP00000443703.1 F5H8C1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399268
Hom.:
0
Cov.:
72
AF XY:
0.00000145
AC XY:
1
AN XY:
690138
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:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.015
.;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.33
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
.;L
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.085
Sift
Uncertain
0.015
D;D
Sift4G
Benign
0.15
T;T
Polyphen
1.0
D;D
Vest4
0.033
MutPred
0.32
Loss of methylation at K1954 (P = 0.0219);Loss of methylation at K1954 (P = 0.0219);
MVP
0.030
ClinPred
0.44
T
GERP RS
2.7
Varity_R
0.13
gMVP
0.034

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50744753; API