13-79481453-C-G

Variant names:

• chr13-79481453-C-G
• rs764185387
• NM_019080.3:c.250C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019080.3(NDFIP2):​c.250C>G​(p.Leu84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. L84F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054389536).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDFIP2	NM_019080.3	MANE Select	c.250C>G	p.Leu84Val	missense	Exon 1 of 8	NP_061953.2	Q9NV92
	NDFIP2	NM_001394685.1		c.250C>G	p.Leu84Val	missense	Exon 1 of 8	NP_001381614.1
	NDFIP2	NM_001161407.2		c.250C>G	p.Leu84Val	missense	Exon 1 of 8	NP_001154879.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDFIP2	ENST00000218652.12	TSL:1 MANE Select	c.250C>G	p.Leu84Val	missense	Exon 1 of 8	ENSP00000218652.7	Q9NV92
	NDFIP2	ENST00000703122.1		c.-33C>G		5_prime_UTR	Exon 1 of 8	ENSP00000515183.1	A0A8V8TQM3
	NDFIP2	ENST00000703126.1		c.-33C>G		5_prime_UTR	Exon 1 of 8	ENSP00000515186.1	A0A8V8TQN2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410678 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 696784

African (AFR) AF: 0.00 AC: 0 AN: 32360

American (AMR) AF: 0.00 AC: 0 AN: 37042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25230

East Asian (EAS) AF: 0.00 AC: 0 AN: 37040

South Asian (SAS) AF: 0.00 AC: 0 AN: 80052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085248

Other (OTH) AF: 0.00 AC: 0 AN: 58448

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.45
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.033
Sift	Benign	0.24	T
Sift4G	Benign	0.57	T
Polyphen		0.0030	B
Vest4		0.071
MutPred		0.13		Gain of catalytic residue at K87 (P = 0.0016)
MVP		0.29
MPC		1.2
ClinPred		0.076	T
GERP RS		3.7
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.087
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs764185387; hg19: chr13-80055588;