rs770517468

Variant names:

• chr2-200892016-C-A
• rs770517468
• NM_001369441.2:c.73C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-200892016-C-A
• chr2-200892016-C-T
• chr2-200892016-C-G

Variant summary

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

The NM_001369441.2(NIF3L1):​c.73C>A​(p.Arg25Ser) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R25C) 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: 1.84
• Publications: 0 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.73C>A	p.Arg25Ser	missense	Exon 2 of 7	NP_001356370.1	Q9GZT8-1
	NIF3L1	NM_001136039.2		c.73C>A	p.Arg25Ser	missense	Exon 2 of 7	NP_001129511.1	Q9GZT8-1
	NIF3L1	NM_001369442.1		c.73C>A	p.Arg25Ser	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.73C>A	p.Arg25Ser	missense	Exon 2 of 7	ENSP00000386394.1	Q9GZT8-1
	NIF3L1	ENST00000409588.1	TSL:1	c.73C>A	p.Arg25Ser	missense	Exon 1 of 5	ENSP00000387021.1	Q9GZT8-3
	NIF3L1	ENST00000359683.8	TSL:1	c.-9C>A		5_prime_UTR	Exon 2 of 7	ENSP00000352711.4	Q9GZT8-2

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	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.062
Sift	Benign	0.044	D
Sift4G	Benign	0.21	T
Polyphen		0.0030	B
Vest4		0.40
MutPred		0.45		Gain of disorder (P = 0.0378)
MVP		0.37
MPC		0.050
ClinPred		0.16	T
GERP RS		3.4
PromoterAI		-0.0023	Neutral
Varity_R		0.12
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.37		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770517468; hg19: chr2-201756739;