13-79481333-A-C

Variant names:

• chr13-79481333-A-C
• rs1161227318
• NM_019080.3:c.130A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019080.3(NDFIP2):​c.130A>C​(p.Thr44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. T44S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2218056).

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.130A>C	p.Thr44Pro	missense	Exon 1 of 8	NP_061953.2	Q9NV92
	NDFIP2	NM_001394685.1		c.130A>C	p.Thr44Pro	missense	Exon 1 of 8	NP_001381614.1
	NDFIP2	NM_001161407.2		c.130A>C	p.Thr44Pro	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.130A>C	p.Thr44Pro	missense	Exon 1 of 8	ENSP00000218652.7	Q9NV92
	NDFIP2	ENST00000703122.1		c.-153A>C		5_prime_UTR	Exon 1 of 8	ENSP00000515183.1	A0A8V8TQM3
	NDFIP2	ENST00000703126.1		c.-153A>C		5_prime_UTR	Exon 1 of 8	ENSP00000515186.1	A0A8V8TQN2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.059
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.27
MutPred		0.13		Loss of phosphorylation at T44 (P = 0.0283)
MVP		0.50
MPC		2.3
ClinPred		0.88	D
GERP RS		3.2
PromoterAI		-0.46	Neutral
Varity_R		0.34
gMVP		0.28
Mutation Taster		=87/13	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: rs1161227318; hg19: chr13-80055468;