16-28951127-C-T

Variant names:

• chr16-28951127-C-T
• rs1964960631
• NM_032815.4:c.116C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032815.4(NFATC2IP):​c.116C>T​(p.Ser39Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,393,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NFATC2IP NM_032815.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.810
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06322852).

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.116C>T	p.Ser39Phe	missense	Exon 1 of 8	NP_116204.3
	NFATC2IP	NM_001394784.1		c.116C>T	p.Ser39Phe	missense	Exon 1 of 7	NP_001381713.1
	NFATC2IP	NM_001394785.1		c.116C>T	p.Ser39Phe	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.116C>T	p.Ser39Phe	missense	Exon 1 of 8	ENSP00000324792.4	Q8NCF5-1
	NFATC2IP	ENST00000564978.5	TSL:1	c.-65+293C>T		intron	N/A	ENSP00000456948.1	H3BSZ7
	NFATC2IP	ENST00000895633.1		c.116C>T	p.Ser39Phe	missense	Exon 1 of 6	ENSP00000565692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1393942 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 687144

African (AFR) AF: 0.0000641 AC: 2 AN: 31204

American (AMR) AF: 0.00 AC: 0 AN: 35472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 35492

South Asian (SAS) AF: 0.00 AC: 0 AN: 78866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076590

Other (OTH) AF: 0.00 AC: 0 AN: 57764

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.81
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.033
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.055	T
Polyphen		0.010	B
Vest4		0.14
MutPred		0.18		Loss of phosphorylation at S39 (P = 0.0061)
MVP		0.17
MPC		0.29
ClinPred		0.22	T
GERP RS		2.0
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.075
gMVP		0.080
Mutation Taster		=88/12	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: rs1964960631; hg19: chr16-28962448; COSMIC: COSV107347366; COSMIC: COSV107347366;