Genetic Variant ENSG00000291186:n.367C>T (chr11-71799562-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000346333.11(ENSG00000291186):n.367C>T variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,710 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: 6.9e-7 ( 0 hom. )

Consequence

ENSG00000291186
ENST00000346333.11 splice_region, non_coding_transcript_exon

Scores

Splicing: ADA: 0.0005198

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.124

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061368197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
FAM86C1P	XR_004643250.2 link	n.917C>T	splice_region_variant, non_coding_transcript_exon_variant	Exon 8 of 8
ALG1L9P	NR_073386.1 link	n.696+3296G>A	intron_variant	Intron 3 of 3
ALG1L9P	NR_073388.1 link	n.696+3296G>A	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000291186	ENST00000346333.11 link	n.367C>T	splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4	1
ENSG00000291186	ENST00000510443.6 link	n.543C>T	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	1
ALG1L9P	ENST00000511954.5 link	n.682+3296G>A	intron_variant	Intron 3 of 3	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726162

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:

8.99e-7

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

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.413C>T (p.A138V) alteration is located in exon 5 (coding exon 5) of the FAM86C1 gene. This alteration results from a C to T substitution at nucleotide position 413, causing the alanine (A) at amino acid position 138 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.9

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0036

.;T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.30

T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

0.26

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.28

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.96

D;P;.

Vest4

0.15

MutPred

0.17

.;Gain of sheet (P = 0.0085);.;

MVP

0.099

MPC

0.22

ClinPred

0.14

GERP RS

2.0

Varity_R

0.033

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over