Genetic Variant ENSG00000291186:n.322C>A (chr11-71796123-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000524714.1(ALG1L9P):n.286G>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 0.00000342 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 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

ALG1L9P
ENST00000524714.1 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.85

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:

Genome browser will be placed here

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=0.07485515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ALG1L9P	NR_073388.1 link	n.699G>T	splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4
FAM86C1P	XR_004643250.2 link	n.872C>A	non_coding_transcript_exon_variant	Exon 7 of 8
ALG1L9P	NR_073386.1 link	n.697-869G>T	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000291186	ENST00000346333.11 link	n.322C>A	non_coding_transcript_exon_variant	Exon 3 of 4	1
ENSG00000291186	ENST00000510443.6 link	n.498C>A	non_coding_transcript_exon_variant	Exon 4 of 5	1
ENSG00000291186	ENST00000526393.5 link	n.478C>A	non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368C>A (p.P123Q) alteration is located in exon 4 (coding exon 4) of the FAM86C1 gene. This alteration results from a C to A substitution at nucleotide position 368, causing the proline (P) at amino acid position 123 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.30

DANN

Benign

0.73

DEOGEN2

Benign

0.0031

.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.37

T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.075

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.65

P;P;.

Vest4

0.26

MutPred

0.19

.;Loss of loop (P = 0.0031);.;

MVP

0.040

MPC

0.56

ClinPred

0.31

GERP RS

-3.0

Varity_R

0.038

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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