NM_032815.4:c.173T>G

Variant names:

• chr16-28951184-T-G
• rs1020176693
• NM_032815.4:c.173T>G

Variant summary

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

The NM_032815.4(NFATC2IP):​c.173T>G​(p.Ile58Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I58L) has been classified 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: 0.256
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071944475).

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.173T>G	p.Ile58Ser	missense	Exon 1 of 8	NP_116204.3
	NFATC2IP	NM_001394784.1		c.173T>G	p.Ile58Ser	missense	Exon 1 of 7	NP_001381713.1
	NFATC2IP	NM_001394785.1		c.173T>G	p.Ile58Ser	missense	Exon 1 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.173T>G	p.Ile58Ser	missense	Exon 1 of 8	ENSP00000324792.4	Q8NCF5-1
	NFATC2IP	ENST00000564978.5	TSL:1	c.-65+350T>G		intron	N/A	ENSP00000456948.1	H3BSZ7
	NFATC2IP	ENST00000895633.1		c.173T>G	p.Ile58Ser	missense	Exon 1 of 6	ENSP00000565692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.26
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.043
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.040	D
Polyphen		0.60	P
Vest4		0.13
MutPred		0.28		Gain of sheet (P = 0.0043)
MVP		0.16
MPC		0.60
ClinPred		0.12	T
GERP RS		1.9
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1020176693; hg19: chr16-28962505;