rs144824716

Variant names:

• chr1-18362168-C-A
• NM_032880.5:c.478C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-18362168-C-A
• chr1-18362168-C-G
• chr1-18362168-C-T

Variant summary

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

The NM_032880.5(IGSF21):​c.478C>A​(p.Arg160Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R160C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IGSF21 NM_032880.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF21	NM_032880.5	c.478C>A	p.Arg160Ser	missense_variant	Exon 5 of 10	ENST00000251296.4	NP_116269.3
IGSF21	XM_017002604.3	c.460C>A	p.Arg154Ser	missense_variant	Exon 5 of 10		XP_016858093.1
IGSF21	XM_017002605.1	c.247C>A	p.Arg83Ser	missense_variant	Exon 4 of 9		XP_016858094.1
IGSF21	XM_011542319.4	c.425-14142C>A		intron_variant	Intron 4 of 7		XP_011540621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF21	ENST00000251296.4	c.478C>A	p.Arg160Ser	missense_variant	Exon 5 of 10	1	NM_032880.5	ENSP00000251296.1
IGSF21	ENST00000412684.3	n.335C>A		non_coding_transcript_exon_variant	Exon 4 of 6	5
IGSF21	ENST00000497331.2	n.802C>A		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460964 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726638

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: 9.00e-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
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.0098	T
Eigen	Benign	0.074
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.42	N
REVEL	Uncertain	0.49
Sift	Benign	0.068	T
Sift4G	Benign	0.21	T
Polyphen		0.34	B
Vest4		0.85
MutPred		0.56		Gain of disorder (P = 0.0504);
MVP		0.92
MPC		0.62
ClinPred		0.80	D
GERP RS		4.6
Varity_R		0.48
gMVP		0.80

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: chr1-18688662;