NM_001004310.3:c.134C>T

Variant summary

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

The NM_001004310.3(FCRL6):​c.134C>T​(p.Thr45Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FCRL6
NM_001004310.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10
Variant links:
Genes affected
FCRL6 (HGNC:31910): (Fc receptor like 6) Enables MHC class II protein binding activity and protein phosphatase binding activity. Predicted to be involved in cell surface receptor signaling pathway. Located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.12615383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FCRL6NM_001004310.3 linkc.134C>T p.Thr45Ile missense_variant Exon 3 of 10 ENST00000368106.4 NP_001004310.2 Q6DN72-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FCRL6ENST00000368106.4 linkc.134C>T p.Thr45Ile missense_variant Exon 3 of 10 1 NM_001004310.3 ENSP00000357086.3 Q6DN72-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251378
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135866
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461308
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
726968
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134C>T (p.T45I) alteration is located in exon 3 (coding exon 3) of the FCRL6 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the threonine (T) at amino acid position 45 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
Benign
0.11
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.34
DANN
Benign
0.94
DEOGEN2
Benign
0.0023
.;.;.;.;T
Eigen
Benign
-0.83
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.0079
N
LIST_S2
Benign
0.47
T;T;T;T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;.;L;L;L
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.8
N;N;N;D;N
REVEL
Benign
0.024
Sift
Benign
0.19
T;T;T;T;T
Sift4G
Benign
0.26
T;T;T;D;T
Polyphen
0.69, 0.24, 0.88, 0.47
.;P;B;P;P
Vest4
0.14, 0.12, 0.13, 0.12
MutPred
0.38
.;.;Loss of ubiquitination at K43 (P = 0.0449);Loss of ubiquitination at K43 (P = 0.0449);Loss of ubiquitination at K43 (P = 0.0449);
MVP
0.14
MPC
0.0088
ClinPred
0.23
T
GERP RS
-1.2
Varity_R
0.030
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs746591505; hg19: chr1-159778049; API