NM_001369441.2:c.293G>T

Variant names:

• chr2-200892236-G-T
• rs770012929
• NM_001369441.2:c.293G>T

Variant summary

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

The NM_001369441.2(NIF3L1):​c.293G>T​(p.Arg98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 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. R98Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIF3L1 NM_001369441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 1 publications found

Genes affected

NIF3L1 (HGNC:13390): (NGG1 interacting factor 3 like 1) Enables identical protein binding activity. Involved in positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369441.2. 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
	NIF3L1	NM_001369441.2	MANE Select	c.293G>T	p.Arg98Leu	missense	Exon 2 of 7	NP_001356370.1	Q9GZT8-1
	NIF3L1	NM_001136039.2		c.293G>T	p.Arg98Leu	missense	Exon 2 of 7	NP_001129511.1	Q9GZT8-1
	NIF3L1	NM_001369442.1		c.293G>T	p.Arg98Leu	missense	Exon 2 of 7	NP_001356371.1	Q9GZT8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIF3L1	ENST00000409020.6	TSL:5 MANE Select	c.293G>T	p.Arg98Leu	missense	Exon 2 of 7	ENSP00000386394.1	Q9GZT8-1
	NIF3L1	ENST00000359683.8	TSL:1	c.212G>T	p.Arg71Leu	missense	Exon 2 of 7	ENSP00000352711.4	Q9GZT8-2
	NIF3L1	ENST00000409588.1	TSL:1	c.293G>T	p.Arg98Leu	missense	Exon 1 of 5	ENSP00000387021.1	Q9GZT8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.86	T
PhyloP100		2.2
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.22
Sift	Benign	0.075	T
Sift4G	Benign	0.14	T
Polyphen		0.0040	B
Vest4		0.41
MutPred		0.75		Loss of MoRF binding (P = 0.01)
MVP		0.40
MPC		0.054
ClinPred		0.45	T
GERP RS		1.5
PromoterAI		-0.0078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs770012929; hg19: chr2-201756959;