NM_001205280.2:c.575G>A

Variant names:

• chr19-44635430-G-A
• NM_001205280.2:c.575G>A

Variant summary

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

The NM_001205280.2(IGSF23):​c.575G>A​(p.Ser192Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 7.2e-7 (0 hom.)
• Consequence: IGSF23 NM_001205280.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

IGSF23 (HGNC:40040): (immunoglobulin superfamily member 23) This gene encodes a protein that has one immunoglobulin (Ig) domain and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Nov 2011]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

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=0.08596662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF23	NM_001205280.2	c.575G>A	p.Ser192Asn	missense_variant	Exon 4 of 5	ENST00000402988.6	NP_001192209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF23	ENST00000402988.6	c.575G>A	p.Ser192Asn	missense_variant	Exon 4 of 5	3	NM_001205280.2	ENSP00000385592.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397122 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689098

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.044
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.93	P
Vest4		0.18
MutPred		0.30		Loss of sheet (P = 0.0817);
MVP		0.12
ClinPred		0.32	T
GERP RS		1.8
Varity_R		0.10
gMVP		0.063

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: chr19-45138730;