chr11-18704529-T-C

Variant summary

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

The NM_173588.4(IGSF22):ā€‹c.3920A>Gā€‹(p.Asp1307Gly) variant causes a missense 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

1
15

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)
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]

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
IGSF22NM_173588.4 linkuse as main transcriptc.3920A>G p.Asp1307Gly missense_variant 23/23 ENST00000513874.6 NP_775859.4
TMEM86ANM_153347.3 linkuse as main transcriptc.*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
IGSF22ENST00000513874.6 linkuse as main transcriptc.3920A>G p.Asp1307Gly missense_variant 23/235 NM_173588.4 ENSP00000421191 P1Q8N9C0-2
TMEM86AENST00000280734.3 linkuse as main transcriptc.*2520T>C 3_prime_UTR_variant 3/31 NM_153347.3 ENSP00000280734 P1
IGSF22ENST00000319338.6 linkuse as main transcriptc.*816A>G 3_prime_UTR_variant, NMD_transcript_variant 21/212 ENSP00000322422 Q8N9C0-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152072
Hom.:
0
Cov.:
32
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:
14
AN:
153656
Hom.:
0
AF XY:
0.0000858
AC XY:
7
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.:
0
Cov.:
28
AF XY:
0.000139
AC XY:
96
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:
8
AN:
152072
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
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.:
0
Bravo
AF:
0.000110
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000883
AC:
2

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 submitterclinical testingAmbry GeneticsAug 23, 2021The 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
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Uncertain
0.99
Eigen
Benign
-0.022
Eigen_PC
Benign
0.066
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;D
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.11
Sift
Benign
0.031
D
Sift4G
Benign
0.17
T
Vest4
0.39
MutPred
0.30
Gain of MoRF binding (P = 0.0833);
MVP
0.38
MPC
0.35
ClinPred
0.14
T
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.

Other links and lift over

dbSNP: rs772744685; hg19: chr11-18726076; API