rs933925607

Variant names:

• chr11-18704503-C-T
• rs933925607
• NM_173588.4:c.3946G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-18704503-C-T
• chr11-18704503-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173588.4(IGSF22):​c.3946G>A​(p.Glu1316Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,550,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10135931).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	NM_173588.4	MANE Select	c.3946G>A	p.Glu1316Lys	missense	Exon 23 of 23	NP_775859.4	Q8N9C0-2
	TMEM86A	NM_153347.3	MANE Select	c.*2494C>T		3_prime_UTR	Exon 3 of 3	NP_699178.1	Q8N2M4
	IGSF22	NR_160413.1		n.3702G>A		non_coding_transcript_exon	Exon 21 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3946G>A	p.Glu1316Lys	missense	Exon 23 of 23	ENSP00000421191.1	Q8N9C0-2
	TMEM86A	ENST00000280734.3	TSL:1 MANE Select	c.*2494C>T		3_prime_UTR	Exon 3 of 3	ENSP00000280734.2	Q8N2M4
	IGSF22	ENST00000319338.6	TSL:2	n.*842G>A		non_coding_transcript_exon	Exon 21 of 21	ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152004 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000260 AC: 4 AN: 153652 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000183

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000168

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.0000329 AC: 46 AN: 1398712 Hom.: 0 Cov.: 29 AF XY: 0.0000391 AC XY: 27 AN XY: 689928

African (AFR) AF: 0.0000317 AC: 1 AN: 31584

American (AMR) AF: 0.0000280 AC: 1 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25182

East Asian (EAS) AF: 0.000672 AC: 24 AN: 35738

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49008

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.0000121 AC: 13 AN: 1078608

Other (OTH) AF: 0.0000690 AC: 4 AN: 57978

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152004 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74238

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	1.0
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.022
Sift	Benign	0.14	T
Sift4G	Benign	0.13	T
Vest4		0.24
MutPred		0.35		Gain of MoRF binding (P = 8e-04)
MVP		0.31
MPC		0.30
ClinPred		0.18	T
GERP RS		4.4
gMVP		0.43
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs933925607; hg19: chr11-18726050; COSMIC: COSV55010505; COSMIC: COSV55010505;