13-79520846-A-T

Variant names:

• chr13-79520846-A-T
• NM_019080.3:c.358A>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.358A>T​(p.Ile120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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]

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=0.04525414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3	c.358A>T	p.Ile120Leu	missense_variant	Exon 2 of 8	ENST00000218652.12	NP_061953.2
NDFIP2	NM_001394685.1	c.355A>T	p.Ile119Leu	missense_variant	Exon 2 of 8		NP_001381614.1
NDFIP2	NM_001161407.2	c.358A>T	p.Ile120Leu	missense_variant	Exon 2 of 8		NP_001154879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12	c.358A>T	p.Ile120Leu	missense_variant	Exon 2 of 8	1	NM_019080.3	ENSP00000218652.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.14
DANN	Benign	0.82
DEOGEN2	Benign	0.0060	T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.50	T;.;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N;N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.24	.;N;.;.
REVEL	Benign	0.022
Sift	Benign	0.18	.;T;.;.
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.20
MutPred		0.29		Gain of catalytic residue at P123 (P = 0.0016);Gain of catalytic residue at P123 (P = 0.0016);.;.;
MVP		0.25
MPC		0.032
ClinPred		0.057	T
GERP RS		-8.4
Varity_R		0.054
gMVP		0.039

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-80094981;