11-18707941-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173588.4(IGSF22):c.3143G>A(p.Arg1048Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,614,180 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (40 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.541

Genes affected

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

IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

TMEM86A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00561291).
• BP6: Variant 11-18707941-C-T is Benign according to our data. Variant chr11-18707941-C-T is described in ClinVar as [Benign]. Clinvar id is 2641667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF22	NM_173588.4	c.3143G>A	p.Arg1048Gln	missense_variant	20/23	ENST00000513874.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF22	ENST00000513874.6	c.3143G>A	p.Arg1048Gln	missense_variant	20/23	5	NM_173588.4	P1
IGSF22	ENST00000504981.5	n.3483G>A		non_coding_transcript_exon_variant	19/20	1
IGSF22-AS1	ENST00000527285.1	n.729+548C>T		intron_variant, non_coding_transcript_variant		3
IGSF22	ENST00000319338.6	c.*39G>A		3_prime_UTR_variant, NMD_transcript_variant	18/21	2

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 597 AN: 152200 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00653

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00403 AC: 1007 AN: 249578 Hom.: 5 AF XY: 0.00458 AC XY: 620 AN XY: 135404

Gnomad AFR exome AF: 0.000969

Gnomad AMR exome AF: 0.00235

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00650

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00573

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.00543 AC: 7944 AN: 1461862 Hom.: 40 Cov.: 32 AF XY: 0.00551 AC XY: 4004 AN XY: 727228

Gnomad4 AFR exome AF: 0.000836

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00711

Gnomad4 FIN exome AF: 0.00219

Gnomad4 NFE exome AF: 0.00612

Gnomad4 OTH exome AF: 0.00426

GnomAD4 genome AF: 0.00393 AC: 598 AN: 152318 Hom.: 7 Cov.: 33 AF XY: 0.00367 AC XY: 273 AN XY: 74486

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00653

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00505 Hom.: 3

Bravo AF: 0.00379

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00149 AC: 6

ESP6500EA AF: 0.00657 AC: 55

ExAC AF: 0.00443 AC: 536

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

IGSF22: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	17
Dann	Uncertain	1.0
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.040	D
Vest4		0.39
MVP		0.24
MPC		0.31
ClinPred		0.023	T
GERP RS		1.8
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs146342750; hg19: chr11-18729488;