rs7917

Variant names:

• chr2-200903515-C-T
• rs7917
• NM_001369441.2:c.971C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369441.2(NIF3L1):​c.971C>T​(p.Thr324Ile) variant causes a missense change. The variant allele was found at a frequency of 0.227 in 1,611,958 control chromosomes in the GnomAD database, including 48,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (9944 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38689 hom.)
• Consequence: NIF3L1 NM_001369441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91
• Publications: 39 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4081597E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

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.971C>T	p.Thr324Ile	missense	Exon 7 of 7	NP_001356370.1	Q9GZT8-1
	NIF3L1	NM_001136039.2		c.971C>T	p.Thr324Ile	missense	Exon 7 of 7	NP_001129511.1	Q9GZT8-1
	NIF3L1	NM_001369442.1		c.971C>T	p.Thr324Ile	missense	Exon 7 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.971C>T	p.Thr324Ile	missense	Exon 7 of 7	ENSP00000386394.1	Q9GZT8-1
	NIF3L1	ENST00000359683.8	TSL:1	c.890C>T	p.Thr297Ile	missense	Exon 7 of 7	ENSP00000352711.4	Q9GZT8-2
	NIF3L1	ENST00000409588.1	TSL:1	c.832C>T	p.Leu278Phe	missense	Exon 5 of 5	ENSP00000387021.1	Q9GZT8-3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47812 AN: 151950 Hom.: 9920 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.214 AC: 53455 AN: 249492 AF XY: 0.211

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.00801

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.218 AC: 318064 AN: 1459890 Hom.: 38689 Cov.: 32 AF XY: 0.216 AC XY: 157064 AN XY: 726264

African (AFR) AF: 0.599 AC: 20020 AN: 33428

American (AMR) AF: 0.147 AC: 6592 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8309 AN: 26118

East Asian (EAS) AF: 0.00507 AC: 201 AN: 39680

South Asian (SAS) AF: 0.168 AC: 14491 AN: 86232

European-Finnish (FIN) AF: 0.211 AC: 11266 AN: 53420

Middle Eastern (MID) AF: 0.212 AC: 1224 AN: 5764

European-Non Finnish (NFE) AF: 0.218 AC: 242158 AN: 1110200

Other (OTH) AF: 0.229 AC: 13803 AN: 60332

GnomAD4 genome AF: 0.315 AC: 47891 AN: 152068 Hom.: 9944 Cov.: 32 AF XY: 0.310 AC XY: 23022 AN XY: 74360

African (AFR) AF: 0.591 AC: 24480 AN: 41446

American (AMR) AF: 0.206 AC: 3142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3470

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5182

South Asian (SAS) AF: 0.155 AC: 747 AN: 4824

European-Finnish (FIN) AF: 0.206 AC: 2175 AN: 10572

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15270 AN: 67986

Other (OTH) AF: 0.290 AC: 611 AN: 2108

Alfa AF: 0.249 Hom.: 19591

Bravo AF: 0.326

TwinsUK AF: 0.214 AC: 793

ALSPAC AF: 0.218 AC: 841

ESP6500AA AF: 0.579 AC: 2196

ESP6500EA AF: 0.221 AC: 1824

ExAC AF: 0.222 AC: 26806

Asia WGS AF: 0.140 AC: 488 AN: 3478

EpiCase AF: 0.220

EpiControl AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.86
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.00014	T
MetaSVM	Benign	-0.95	T
PhyloP100		5.9
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.14
Sift	Benign	0.82	T
Sift4G	Benign	0.65	T
Vest4		0.10
ClinPred		0.036	T
GERP RS		5.3
Varity_R		0.027
Mutation Taster		=93/7	polymorphism (auto)

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: rs7917; hg19: chr2-201768238; COSMIC: COSV62900214; COSMIC: COSV62900214;