19-44613695-G-C

Position:

• chr19-44613695-G-C

Variant summary

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

The NM_001205280.2(IGSF23):​c.50G>C​(p.Trp17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGSF23 NM_001205280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.295

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]

CEACAM22P (HGNC:38029): (CEA cell adhesion molecule 22, pseudogene)

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=0.08700168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF23	NM_001205280.2	c.50G>C	p.Trp17Ser	missense_variant	1/5	ENST00000402988.6	NP_001192209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF23	ENST00000402988.6	c.50G>C	p.Trp17Ser	missense_variant	1/5	3	NM_001205280.2	ENSP00000385592	P1
CEACAM22P	ENST00000455455.1	n.57+7070C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.50G>C (p.W17S) alteration is located in exon 1 (coding exon 1) of the IGSF23 gene. This alteration results from a G to C substitution at nucleotide position 50, causing the tryptophan (W) at amino acid position 17 to be replaced by a serine (S). 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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.71
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.20
MutPred		0.13		Gain of glycosylation at W17 (P = 7e-04);
MVP		0.43
ClinPred		0.23	T
GERP RS		-0.30
Varity_R		0.094
gMVP		0.23

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: rs1481579100; hg19: chr19-45117005;