2-200892247-C-T

Variant names:

• chr2-200892247-C-T
• rs34907463
• NM_001369441.2:c.304C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001369441.2(NIF3L1):​c.304C>T​(p.Arg102Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00051 in 1,614,162 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts 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. R102H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (3 hom.)
• Consequence: NIF3L1 NM_001369441.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84
• Publications: 5 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04540813).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.304C>T	p.Arg102Cys	missense	Exon 2 of 7	NP_001356370.1	Q9GZT8-1
	NIF3L1	NM_001136039.2		c.304C>T	p.Arg102Cys	missense	Exon 2 of 7	NP_001129511.1	Q9GZT8-1
	NIF3L1	NM_001369442.1		c.304C>T	p.Arg102Cys	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.304C>T	p.Arg102Cys	missense	Exon 2 of 7	ENSP00000386394.1	Q9GZT8-1
	NIF3L1	ENST00000359683.8	TSL:1	c.223C>T	p.Arg75Cys	missense	Exon 2 of 7	ENSP00000352711.4	Q9GZT8-2
	NIF3L1	ENST00000409588.1	TSL:1	c.304C>T	p.Arg102Cys	missense	Exon 1 of 5	ENSP00000387021.1	Q9GZT8-3

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000473 AC: 118 AN: 249430 AF XY: 0.000451

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.000733

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000526 AC: 769 AN: 1461826 Hom.: 3 Cov.: 31 AF XY: 0.000531 AC XY: 386 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 53 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000525 AC: 28 AN: 53366

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000588 AC: 654 AN: 1112000

Other (OTH) AF: 0.000497 AC: 30 AN: 60394

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000820 Hom.: 0

Bravo AF: 0.000340

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000844 AC: 7

ExAC AF: 0.000488 AC: 59

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.000652

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	0.082
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.52	T
PhyloP100		3.8
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.38
MVP		0.64
MPC		0.067
ClinPred		0.24	T
GERP RS		3.1
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.61
Mutation Taster		=98/2	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: rs34907463; hg19: chr2-201756970; COSMIC: COSV53770281; COSMIC: COSV53770281;