13-79481214-G-T

Variant names:

• chr13-79481214-G-T
• rs535539840
• NM_019080.3:c.11G>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.11G>T​(p.Arg4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,355,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=0.14610896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 8	ENST00000218652.12	NP_061953.2
NDFIP2	NM_001394685.1	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 8		NP_001381614.1
NDFIP2	NM_001161407.2	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 8		NP_001154879.1
NDFIP2-AS1	NR_046685.1	n.18C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 8	1	NM_019080.3	ENSP00000218652.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000949 AC: 1 AN: 105362 Hom.: 0 AF XY: 0.0000171 AC XY: 1 AN XY: 58334

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: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000811 AC: 11 AN: 1355914 Hom.: 0 Cov.: 31 AF XY: 0.00000899 AC XY: 6 AN XY: 667516

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: 0.0000266

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000749

Gnomad4 OTH exome AF: 0.0000177

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0062	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.65	.;N
REVEL	Benign	0.15
Sift	Benign	0.092	.;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.68	P;P
Vest4		0.18
MutPred		0.32		Gain of catalytic residue at R8 (P = 0.0223);Gain of catalytic residue at R8 (P = 0.0223);
MVP		0.54
MPC		1.4
ClinPred		0.48	T
GERP RS		3.8
Varity_R		0.060
gMVP		0.49

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: rs535539840; hg19: chr13-80055349;