Genetic Variant ENSG00000291186:n.253C>T (chr11-71796054-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.253C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000291186
ENST00000346333.11 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

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 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=0.060628563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ALG1L9P	NR_073388.1 link	n.768G>A	non_coding_transcript_exon_variant	Exon 4 of 4
FAM86C1P	XR_004643250.2 link	n.803C>T	non_coding_transcript_exon_variant	Exon 7 of 8
ALG1L9P	NR_073386.1 link	n.697-800G>A	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000291186	ENST00000346333.11 link	n.253C>T	non_coding_transcript_exon_variant	Exon 3 of 4	1
ENSG00000291186	ENST00000510443.6 link	n.429C>T	non_coding_transcript_exon_variant	Exon 4 of 5	1
ENSG00000291186	ENST00000526393.5 link	n.409C>T	non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152266

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250818

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460712

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.299C>T (p.S100L) alteration is located in exon 4 (coding exon 4) of the FAM86C1 gene. This alteration results from a C to T substitution at nucleotide position 299, causing the serine (S) at amino acid position 100 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.8

DANN

Benign

0.95

DEOGEN2

Benign

0.0072

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.47

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.041

Sift

Uncertain

0.0030

D;D;T

Sift4G

Uncertain

0.0090

D;T;T

Polyphen

0.0030

B;B;.

Vest4

0.21

MutPred

0.26

.;Loss of disorder (P = 0.0336);.;

MVP

0.076

MPC

0.76

ClinPred

0.27

GERP RS

-0.66

Varity_R

0.16

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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