Genetic Variant ENSG00000291186:n.270C>T (chr11-71793380-C-T) – ACMG Classification: Uncertain_significance (1 pts)

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

Splicing: ADA: 0.003526

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

ENSG00000291186 (HGNC:):

ENSG00000291186 links:

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]

FAM86C1P links:

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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
FAM86C1P	XR_004643250.2 link	n.264C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000291186	ENST00000526393.5 link	n.270C>T	splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 5	1
ENSG00000291186	ENST00000346333.11 link	n.216-2637C>T	intron_variant	Intron 2 of 3	1
ENSG00000291186	ENST00000510443.6 link	n.391+1561C>T	intron_variant	Intron 3 of 4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.096

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.089

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.62

M_CAP

Benign

0.0051

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.97

Vest4

0.38

MutPred

0.49

Loss of disorder (P = 0.0362);

MVP

0.17

MPC

0.77

ClinPred

0.96

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over