Genetic Variant NDFIP2:p.Ser85Cys (chr13-79481457-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019080.3(NDFIP2):c.254C>G(p.Ser85Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,410,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NDFIP2
NM_019080.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

1 publications found

Variant links:

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 links:

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

NDFIP2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106612295).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDFIP2	NM_019080.3	MANE Select	c.254C>G	p.Ser85Cys	missense	Exon 1 of 8	NP_061953.2	Q9NV92
NDFIP2	NM_001394685.1		c.254C>G	p.Ser85Cys	missense	Exon 1 of 8	NP_001381614.1
NDFIP2	NM_001161407.2		c.254C>G	p.Ser85Cys	missense	Exon 1 of 8	NP_001154879.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDFIP2	ENST00000218652.12	TSL:1 MANE Select	c.254C>G	p.Ser85Cys	missense	Exon 1 of 8	ENSP00000218652.7	Q9NV92
NDFIP2	ENST00000703122.1		c.-29C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000515183.1	A0A8V8TQM3
NDFIP2	ENST00000703126.1		c.-29C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000515186.1	A0A8V8TQN2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

166754

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000785

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1410980

Hom.:

Cov.:

AF XY:

0.00000430

AC XY:

AN XY:

696978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32376

American (AMR)

AF:

0.0000269

AC:

AN:

37124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25230

East Asian (EAS)

AF:

0.0000540

AC:

AN:

37060

South Asian (SAS)

AF:

0.00

AC:

AN:

80058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

9.21e-7

AC:

AN:

1085378

Other (OTH)

AF:

0.00

AC:

AN:

58460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.54

M_CAP

Benign

0.0082

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.3

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.95

REVEL

Benign

0.039

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.012

Polyphen

0.042

Vest4

0.10

MutPred

0.17

Loss of phosphorylation at S85 (P = 0.0073)

MVP

0.30

MPC

1.3

ClinPred

0.084

GERP RS

3.4

PromoterAI

-0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over