Variant 11-18706117-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173588.4(IGSF22):c.3610T>C(p.Tyr1204His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,544,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

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

IGSF22 links:

IGSF22 (HGNC:):

IGSF22 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=0.033863634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4 linkuse as main transcript	c.3610T>C	p.Tyr1204His	missense_variant	22/23	ENST00000513874.6	NP_775859.4	Q8N9C0-2
IGSF22	XM_047426830.1 linkuse as main transcript	c.1684T>C	p.Tyr562His	missense_variant	9/10		XP_047282786.1
IGSF22	NR_160413.1 linkuse as main transcript	n.3366T>C		non_coding_transcript_exon_variant	20/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF22	ENST00000513874.6 linkuse as main transcript	c.3610T>C	p.Tyr1204His	missense_variant	22/23	5	NM_173588.4	ENSP00000421191.1	Q8N9C0-2
IGSF22	ENST00000319338.6 linkuse as main transcript	n.*506T>C		non_coding_transcript_exon_variant	20/21	2		ENSP00000322422.6	Q8N9C0-1
IGSF22	ENST00000510673.1 linkuse as main transcript	n.13T>C		non_coding_transcript_exon_variant	1/2	3
IGSF22	ENST00000319338.6 linkuse as main transcript	n.*506T>C		3_prime_UTR_variant	20/21	2		ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

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:

0.000478

GnomAD3 exomes

AF:

0.0000341

AC:

AN:

146432

Hom.:

AF XY:

0.0000510

AC XY:

AN XY:

78388

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.0000406

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000223

AC:

AN:

1392258

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

687082

show subpopulations

Gnomad4 AFR exome

AF:

0.000950

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000151

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000530

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:

0.000473

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000268

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

Nov 27, 2024

The c.3610T>C (p.Y1204H) alteration is located in exon 22 (coding exon 21) of the IGSF22 gene. This alteration results from a T to C substitution at nucleotide position 3610, causing the tyrosine (Y) at amino acid position 1204 to be replaced by a histidine (H). 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

-0.45

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.57

M_CAP

Benign

0.023

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.038

Sift

Benign

0.10

Sift4G

Pathogenic

0.0

Vest4

0.31

MVP

0.21

MPC

0.67

ClinPred

0.057

GERP RS

2.4

gMVP

0.48

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

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