13-79481273-C-T

Variant names:

• chr13-79481273-C-T
• rs765339990
• NM_019080.3:c.70C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019080.3(NDFIP2):​c.70C>T​(p.Pro24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,384,988 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056749165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3	c.70C>T	p.Pro24Ser	missense_variant	Exon 1 of 8	ENST00000218652.12	NP_061953.2
NDFIP2	NM_001394685.1	c.70C>T	p.Pro24Ser	missense_variant	Exon 1 of 8		NP_001381614.1
NDFIP2	NM_001161407.2	c.70C>T	p.Pro24Ser	missense_variant	Exon 1 of 8		NP_001154879.1
NDFIP2-AS1	NR_046685.1	n.-42G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12	c.70C>T	p.Pro24Ser	missense_variant	Exon 1 of 8	1	NM_019080.3	ENSP00000218652.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000760 AC: 1 AN: 131636 Hom.: 0 AF XY: 0.0000139 AC XY: 1 AN XY: 71996

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000446

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1384988 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 683328

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: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000109 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.50	T;.
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.92	.;N
REVEL	Benign	0.016
Sift	Uncertain	0.016	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0030	B;B
Vest4		0.063
MutPred		0.21		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.25
MPC		1.2
ClinPred		0.14	T
GERP RS		0.69
Varity_R		0.058
gMVP		0.23

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: rs765339990; hg19: chr13-80055408;