NM_019080.3:c.85G>T

Variant names:

• chr13-79481288-G-T
• rs1475807175
• NM_019080.3:c.85G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019080.3(NDFIP2):​c.85G>T​(p.Gly29*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDFIP2 NM_019080.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.85G>T	p.Gly29*	stop_gained	Exon 1 of 8	NP_061953.2	Q9NV92
	NDFIP2	NM_001394685.1		c.85G>T	p.Gly29*	stop_gained	Exon 1 of 8	NP_001381614.1
	NDFIP2	NM_001161407.2		c.85G>T	p.Gly29*	stop_gained	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.85G>T	p.Gly29*	stop_gained	Exon 1 of 8	ENSP00000218652.7	Q9NV92
	NDFIP2	ENST00000703122.1		c.-198G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000515183.1	A0A8V8TQM3
	NDFIP2	ENST00000703126.1		c.-198G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000515186.1	A0A8V8TQN2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 133068 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1386988 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684346

African (AFR) AF: 0.00 AC: 0 AN: 31528

American (AMR) AF: 0.00 AC: 0 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078254

Other (OTH) AF: 0.00 AC: 0 AN: 57836

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Benign	0.97
Eigen	Benign	0.061
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.064	N
PhyloP100		-0.41
Vest4		0.29
GERP RS		0.069
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=32/168	disease causing (fs/PTC)

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: rs1475807175; hg19: chr13-80055423;