rs1020176693

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-28951184-T-C
• chr16-28951184-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032815.4(NFATC2IP):​c.173T>C​(p.Ile58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,389,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. I58S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: NFATC2IP NM_032815.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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

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=0.025966465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC2IP	NM_032815.4	c.173T>C	p.Ile58Thr	missense_variant	Exon 1 of 8	ENST00000320805.9	NP_116204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2IP	ENST00000320805.9	c.173T>C	p.Ile58Thr	missense_variant	Exon 1 of 8	1	NM_032815.4	ENSP00000324792.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.000228 AC: 33 AN: 144430 Hom.: 0 AF XY: 0.000193 AC XY: 15 AN XY: 77688

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000244

GnomAD4 exome AF: 0.0000274 AC: 38 AN: 1389070 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 16 AN XY: 684262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.31e-7

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.022
Sift	Benign	0.049	D
Sift4G	Benign	0.14	T
Polyphen		0.42	B
Vest4		0.12
MutPred		0.26		Gain of sheet (P = 0.0043);
MVP		0.16
MPC		0.42
ClinPred		0.025	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
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

LitVar

Other links and lift over

dbSNP: rs1020176693; hg19: chr16-28962505;