Genetic Variant ENSG00000291186:n.363T>C (chr11-71796164-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000346333.11(ENSG00000291186):n.363T>C variant causes a splice region, non coding transcript exon change. The variant allele was found at a frequency of 0.00000342 in 1,461,548 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: 36)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ENSG00000291186
ENST00000346333.11 splice_region, non_coding_transcript_exon

Scores

Splicing: ADA: 0.0003771

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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:

ALG1L9P (HGNC:44378): (ALG1 like 9, pseudogene)

ALG1L9P links:

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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=0.11052725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
FAM86C1P	XR_004643250.2 link	n.913T>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 8
ALG1L9P	NR_073386.1 link	n.697-910A>G	intron_variant	Intron 3 of 3
ALG1L9P	NR_073388.1 link	n.697-39A>G	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000291186	ENST00000346333.11 link	n.363T>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 4	1
ENSG00000291186	ENST00000510443.6 link	n.539T>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 5	1
ENSG00000291186	ENST00000526393.5 link	n.519T>C	non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727074

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

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

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.409T>C (p.Y137H) alteration is located in exon 4 (coding exon 4) of the FAM86C1 gene. This alteration results from a T to C substitution at nucleotide position 409, causing the tyrosine (Y) at amino acid position 137 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0054

.;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.32

T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.72

N;N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.24

B;B;.

Vest4

0.24

MutPred

0.28

.;Loss of phosphorylation at Y137 (P = 0.0363);.;

MVP

0.10

MPC

0.60

ClinPred

0.21

GERP RS

1.5

Varity_R

0.23

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00038

dbscSNV1_RF

Benign

0.030

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

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