chr11-71793380-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000526393.5(ENSG00000291186):​n.270C>T variant causes a splice region, non coding transcript exon change. The variant allele was found at a frequency of 0.00000137 in 1,458,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ENSG00000291186
ENST00000526393.5 splice_region, non_coding_transcript_exon

Scores

2
5
11
Splicing: ADA: 0.003526
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73
Variant links:
Genes affected
FAM86C1P (HGNC:25561): (family with sequence similarity 86 member C1, pseudogene) Predicted to enable protein-L-histidine N-tele-methyltransferase activity. Predicted to be involved in peptidyl-histidine methylation, to form tele-methylhistidine. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2738064).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM86C1PXR_004643250.2 linkn.264C>T splice_region_variant, non_coding_transcript_exon_variant Exon 4 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000291186ENST00000526393.5 linkn.270C>T splice_region_variant, non_coding_transcript_exon_variant Exon 4 of 5 1
ENSG00000291186ENST00000346333.11 linkn.216-2637C>T intron_variant Intron 2 of 3 1
ENSG00000291186ENST00000510443.6 linkn.391+1561C>T intron_variant Intron 3 of 4 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458742
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725706
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.160C>T (p.H54Y) alteration is located in exon 3 (coding exon 3) of the FAM86C1 gene. This alteration results from a C to T substitution at nucleotide position 160, causing the histidine (H) at amino acid position 54 to be replaced by a tyrosine (Y). 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
0.22
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.096
T
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.089
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.97
D
Vest4
0.38
MutPred
0.49
Loss of disorder (P = 0.0362);
MVP
0.17
MPC
0.77
ClinPred
0.96
D
GERP RS
2.0
Varity_R
0.47
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0035
dbscSNV1_RF
Benign
0.17
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: rs1951779436; hg19: chr11-71504426; API