1-18334960-C-A

Variant names:

• chr1-18334960-C-A
• rs1170346511
• NM_032880.5:c.374C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032880.5(IGSF21):​c.374C>A​(p.Thr125Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T125A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGSF21 NM_032880.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.20
• Publications: 2 publications found

Genes affected

IGSF21 (HGNC:28246): (immunoglobin superfamily member 21) This gene encodes a protein which has two immunoglobulin (Ig) domains 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, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032880.5. 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
	IGSF21	NM_032880.5	MANE Select	c.374C>A	p.Thr125Asn	missense	Exon 4 of 10	NP_116269.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF21	ENST00000251296.4	TSL:1 MANE Select	c.374C>A	p.Thr125Asn	missense	Exon 4 of 10	ENSP00000251296.1	Q96ID5
	IGSF21	ENST00000931381.1		c.374C>A	p.Thr125Asn	missense	Exon 4 of 10	ENSP00000601440.1
	IGSF21	ENST00000873158.1		c.374C>A	p.Thr125Asn	missense	Exon 4 of 10	ENSP00000543217.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251130 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.94	P
Vest4		0.82
MutPred		0.32		Loss of phosphorylation at T125 (P = 0.0787)
MVP		0.29
MPC		0.89
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.62
Mutation Taster		=50/50

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: rs1170346511; hg19: chr1-18661454;