Variant 11-18704529-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000280734.3(TMEM86A):c.*2520T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,548,686 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TMEM86A
ENST00000280734.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

IGSF22 (HGNC:26750): (immunoglobulin superfamily member 22)

IGSF22 links:

TMEM86A (HGNC:26890): (transmembrane protein 86A) Predicted to enable alkenylglycerophosphocholine hydrolase activity and alkenylglycerophosphoethanolamine hydrolase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM86A 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=0.16289163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4 linkuse as main transcript	c.3920A>G	p.Asp1307Gly	missense_variant	23/23	ENST00000513874.6	NP_775859.4
TMEM86A	NM_153347.3 linkuse as main transcript	c.*2520T>C		3_prime_UTR_variant	3/3	ENST00000280734.3	NP_699178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6 linkuse as main transcript	c.3920A>G	p.Asp1307Gly	missense_variant	23/23	5	NM_173588.4	ENSP00000421191	P1	Q8N9C0-2
TMEM86A	ENST00000280734.3 linkuse as main transcript	c.*2520T>C		3_prime_UTR_variant	3/3	1	NM_153347.3	ENSP00000280734	P1
IGSF22	ENST00000319338.6 linkuse as main transcript	c.*816A>G		3_prime_UTR_variant, NMD_transcript_variant	21/21	2		ENSP00000322422		Q8N9C0-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000911

AC:

AN:

153656

Hom.:

AF XY:

0.0000858

AC XY:

AN XY:

81574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000140

AC:

195

AN:

1396614

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

689072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000206

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000982

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000883

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.3920A>G (p.D1307G) alteration is located in exon 23 (coding exon 22) of the IGSF22 gene. This alteration results from a A to G substitution at nucleotide position 3920, causing the aspartic acid (D) at amino acid position 1307 to be replaced by a glycine (G). 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

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.022

Eigen_PC

Benign

0.066

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.47

M_CAP

Benign

0.012

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

0.031

Sift4G

Benign

0.17

Vest4

0.39

MutPred

0.30

Gain of MoRF binding (P = 0.0833);

MVP

0.38

MPC

0.35

ClinPred

0.14

GERP RS

4.3

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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