16-28952199-A-C

Variant names:

• chr16-28952199-A-C
• NM_032815.4:c.455A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032815.4(NFATC2IP):​c.455A>C​(p.Glu152Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFATC2IP NM_032815.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74
• Publications: 0 publications found

Genes affected

NFATC2IP (HGNC:25906): (nuclear factor of activated T cells 2 interacting protein) Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2846849).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032815.4. 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
	NFATC2IP	NM_032815.4	MANE Select	c.455A>C	p.Glu152Ala	missense	Exon 2 of 8	NP_116204.3
	NFATC2IP	NM_001394784.1		c.455A>C	p.Glu152Ala	missense	Exon 2 of 7	NP_001381713.1
	NFATC2IP	NM_001394785.1		c.455A>C	p.Glu152Ala	missense	Exon 2 of 6	NP_001381714.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2IP	ENST00000320805.9	TSL:1 MANE Select	c.455A>C	p.Glu152Ala	missense	Exon 2 of 8	ENSP00000324792.4	Q8NCF5-1
	NFATC2IP	ENST00000564978.5	TSL:1	c.4A>C	p.Arg2Arg	synonymous	Exon 2 of 5	ENSP00000456948.1	H3BSZ7
	NFATC2IP	ENST00000895633.1		c.455A>C	p.Glu152Ala	missense	Exon 2 of 6	ENSP00000565692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.068
Sift	Uncertain	0.029	D
Sift4G	Benign	0.12	T
Polyphen		0.94	P
Vest4		0.45
MutPred		0.20		Loss of sheet (P = 0.0104)
MVP		0.35
MPC		0.96
ClinPred		0.70	D
GERP RS		3.5
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.8
Varity_R		0.099
gMVP		0.19

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

hg19: chr16-28963520;