11-18704503-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173588.4(IGSF22):​c.3946G>C​(p.Glu1316Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,712 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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

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=0.13624853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.3946G>C	p.Glu1316Gln	missense_variant	Exon 23 of 23	ENST00000513874.6	NP_775859.4
TMEM86A	NM_153347.3	c.*2494C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000280734.3	NP_699178.1
IGSF22	XM_047426830.1	c.2020G>C	p.Glu674Gln	missense_variant	Exon 10 of 10		XP_047282786.1
IGSF22	NR_160413.1	n.3702G>C		non_coding_transcript_exon_variant	Exon 21 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.3946G>C	p.Glu1316Gln	missense_variant	Exon 23 of 23	5	NM_173588.4	ENSP00000421191.1
TMEM86A	ENST00000280734.3	c.*2494C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_153347.3	ENSP00000280734.2
IGSF22	ENST00000319338.6	n.*842G>C		non_coding_transcript_exon_variant	Exon 21 of 21	2		ENSP00000322422.6
IGSF22	ENST00000319338.6	n.*842G>C		3_prime_UTR_variant	Exon 21 of 21	2		ENSP00000322422.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398712 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 689928

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.082
Eigen_PC	Benign	-0.098
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.062
Sift	Benign	0.16	T
Sift4G	Benign	0.14	T
Vest4		0.15
MutPred		0.26		Gain of MoRF binding (P = 0.02);
MVP		0.37
MPC		0.40
ClinPred		0.43	T
GERP RS		4.4
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18726050;