13-79481331-C-G

Variant names:

• chr13-79481331-C-G
• NM_019080.3:c.128C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_019080.3(NDFIP2):​c.128C>G​(p.Ala43Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDFIP2 NM_019080.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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 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=0.13402432).
• BP6: Variant 13-79481331-C-G is Benign according to our data. Variant chr13-79481331-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3403727.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3	c.128C>G	p.Ala43Gly	missense_variant	Exon 1 of 8	ENST00000218652.12	NP_061953.2
NDFIP2	NM_001394685.1	c.128C>G	p.Ala43Gly	missense_variant	Exon 1 of 8		NP_001381614.1
NDFIP2	NM_001161407.2	c.128C>G	p.Ala43Gly	missense_variant	Exon 1 of 8		NP_001154879.1
NDFIP2-AS1	NR_046685.1	n.-100G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12	c.128C>G	p.Ala43Gly	missense_variant	Exon 1 of 8	1	NM_019080.3	ENSP00000218652.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0098	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.46	T;.
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.56	.;N
REVEL	Benign	0.048
Sift	Benign	0.14	.;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.49	P;P
Vest4		0.12
MutPred		0.18		Gain of catalytic residue at T44 (P = 9e-04);Gain of catalytic residue at T44 (P = 9e-04);
MVP		0.30
MPC		1.1
ClinPred		0.15	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.046
gMVP		0.13

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: chr13-80055466;