13-79481285-C-T

Variant names:

• chr13-79481285-C-T
• rs1244039337
• NM_019080.3:c.82C>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.82C>T​(p.Arg28Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000649 in 1,386,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 31)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.108

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=0.124240786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3	c.82C>T	p.Arg28Cys	missense_variant	Exon 1 of 8	ENST00000218652.12	NP_061953.2
NDFIP2	NM_001394685.1	c.82C>T	p.Arg28Cys	missense_variant	Exon 1 of 8		NP_001381614.1
NDFIP2	NM_001161407.2	c.82C>T	p.Arg28Cys	missense_variant	Exon 1 of 8		NP_001154879.1
NDFIP2-AS1	NR_046685.1	n.-54G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12	c.82C>T	p.Arg28Cys	missense_variant	Exon 1 of 8	1	NM_019080.3	ENSP00000218652.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000649 AC: 9 AN: 1386452 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 684070

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000649

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82C>T (p.R28C) alteration is located in exon 1 (coding exon 1) of the NDFIP2 gene. This alteration results from a C to T substitution at nucleotide position 82, causing the arginine (R) at amino acid position 28 to be replaced by a cysteine (C). 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	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0084	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.57	T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.81	.;N
REVEL	Benign	0.061
Sift	Uncertain	0.017	.;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.98	D;D
Vest4		0.11
MutPred		0.36		Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);
MVP		0.24
MPC		1.9
ClinPred		0.37	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.16

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: rs1244039337; hg19: chr13-80055420;