rs114915440

Variant names:

• chr1-116579663-G-A
• rs114915440
• NM_001007237.3:c.3063C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-116579663-G-A
• chr1-116579663-G-C
• chr1-116579663-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001007237.3(IGSF3):​c.3063C>T​(p.Asp1021Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,565,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: IGSF3 NM_001007237.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

IGSF3 (HGNC:5950): (immunoglobulin superfamily member 3) The protein encoded by this gene is an immunoglobulin-like membrane protein containing several V-type Ig-like domains. A mutation in this gene has been associated with bilateral nasolacrimal duct obstruction (LCDD). [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF3	NM_001007237.3	c.3063C>T	p.Asp1021Asp	synonymous_variant	Exon 10 of 11	ENST00000369486.8	NP_001007238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF3	ENST00000369486.8	c.3063C>T	p.Asp1021Asp	synonymous_variant	Exon 10 of 11	1	NM_001007237.3	ENSP00000358498.4
IGSF3	ENST00000318837.6	c.3123C>T	p.Asp1041Asp	synonymous_variant	Exon 10 of 11	2		ENSP00000321184.6
IGSF3	ENST00000369483.5	c.3123C>T	p.Asp1041Asp	synonymous_variant	Exon 11 of 12	5		ENSP00000358495.1

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150386 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000934 AC: 2 AN: 214242 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 115596

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000631

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000134 AC: 19 AN: 1414670 Hom.: 0 Cov.: 40 AF XY: 0.0000185 AC XY: 13 AN XY: 703500

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.0000462

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000112

Gnomad4 OTH exome AF: 0.0000341

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150386 Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1 AN XY: 73366

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.63

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: rs114915440; hg19: chr1-117122285; COSMIC: COSV59592742;