1-185307066-A-C

Position:

• chr1-185307066-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP3

The NM_006469.5(IVNS1ABP):​c.605T>G​(p.Val202Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IVNS1ABP NM_006469.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.16

Genes affected

IVNS1ABP (HGNC:16951): (influenza virus NS1A binding protein) Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, IVNS1ABP
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IVNS1ABP	NM_006469.5	c.605T>G	p.Val202Gly	missense_variant	7/15	ENST00000367498.8
IVNS1ABP	XM_047434070.1	c.605T>G	p.Val202Gly	missense_variant	7/15
IVNS1ABP	XM_047434096.1	c.338T>G	p.Val113Gly	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IVNS1ABP	ENST00000367498.8	c.605T>G	p.Val202Gly	missense_variant	7/15	1	NM_006469.5	P1
IVNS1ABP	ENST00000422754.1	c.248T>G	p.Val83Gly	missense_variant	2/2	2
IVNS1ABP	ENST00000459929.5	n.1172T>G		non_coding_transcript_exon_variant	7/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 03, 2022

The c.605T>G (p.V202G) alteration is located in exon 7 (coding exon 5) of the IVNS1ABP gene. This alteration results from a T to G substitution at nucleotide position 605, causing the valine (V) at amino acid position 202 to be replaced by a glycine (G). 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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.80	D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.036
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.012	B;.
Vest4		0.67
MutPred		0.64		Loss of stability (P = 0.0039);.;
MVP		0.80
MPC		0.84
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.84
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-185276198;