NM_019080.3:c.269C>T

Variant names:

• chr13-79481472-C-T
• rs1229673695
• NM_019080.3:c.269C>T

Variant summary

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

The NM_019080.3(NDFIP2):​c.269C>T​(p.Pro90Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

Genes affected

NDFIP2 (HGNC:18537): (Nedd4 family interacting protein 2) Enables WW domain binding activity. Involved in negative regulation of gene expression; negative regulation of transport; and positive regulation of protein ubiquitination. Located in several cellular components, including Golgi apparatus; mitochondrion; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NDFIP2-AS1 (HGNC:40844): (NDFIP2 antisense RNA 1)

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=0.08485004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 8	ENST00000218652.12	NP_061953.2
NDFIP2	NM_001394685.1	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 8		NP_001381614.1
NDFIP2	NM_001161407.2	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 8		NP_001154879.1
NDFIP2-AS1	NR_046685.1	n.-241G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 8	1	NM_019080.3	ENSP00000218652.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1410378 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696692

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: 0.00

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	Benign	0.081
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.70	T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.071
Sift	Uncertain	0.0090	.;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.21		Gain of catalytic residue at M95 (P = 0.008);Gain of catalytic residue at M95 (P = 0.008);
MVP		0.29
MPC		1.2
ClinPred		0.51	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.26

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: rs1229673695; hg19: chr13-80055607;