rs12919

Variant names:

• chr7-156969554-G-A
• rs12919
• NM_138400.2:c.2434G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-156969554-G-A
• chr7-156969554-G-C
• chr7-156969554-G-T

Variant summary

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

The NM_138400.2(NOM1):​c.2434G>A​(p.Val812Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,612,708 control chromosomes in the GnomAD database, including 239,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.53 (21908 hom., cov: 32)
  • Exomes 𝑓: 0.54 (218020 hom.)
• Consequence: NOM1 NM_138400.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 43 publications found

Genes affected

NOM1 (HGNC:13244): (nucleolar protein with MIF4G domain 1) Proteins that contain MIF4G (middle of eIF4G (MIM 600495)) and/or MA3 domains, such as NOM1, function in protein translation. These domains include binding sites for members of the EIF4A family of ATP-dependent DEAD box RNA helicases (see EIF4A1; MIM 602641) (Simmons et al., 2005 [PubMed 15715967]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.544928E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138400.2. 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
	NOM1	NM_138400.2	MANE Select	c.2434G>A	p.Val812Met	missense	Exon 11 of 11	NP_612409.1	Q5C9Z4
	NOM1	NM_001353366.2		c.2437G>A	p.Val813Met	missense	Exon 11 of 11	NP_001340295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOM1	ENST00000275820.4	TSL:1 MANE Select	c.2434G>A	p.Val812Met	missense	Exon 11 of 11	ENSP00000275820.3	Q5C9Z4
	NOM1	ENST00000851672.1		c.2437G>A	p.Val813Met	missense	Exon 11 of 11	ENSP00000521731.1
	NOM1	ENST00000851673.1		c.2233G>A	p.Val745Met	missense	Exon 11 of 11	ENSP00000521732.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80951 AN: 151932 Hom.: 21900 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.581

GnomAD2 exomes AF: 0.516 AC: 129185 AN: 250510 AF XY: 0.515

Gnomad AFR exome AF: 0.534

Gnomad AMR exome AF: 0.538

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.281

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.543 AC: 793137 AN: 1460658 Hom.: 218020 Cov.: 42 AF XY: 0.541 AC XY: 393192 AN XY: 726618

African (AFR) AF: 0.534 AC: 17858 AN: 33458

American (AMR) AF: 0.540 AC: 24087 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16277 AN: 26114

East Asian (EAS) AF: 0.281 AC: 11159 AN: 39680

South Asian (SAS) AF: 0.467 AC: 40194 AN: 86158

European-Finnish (FIN) AF: 0.458 AC: 24419 AN: 53286

Middle Eastern (MID) AF: 0.631 AC: 3630 AN: 5754

European-Non Finnish (NFE) AF: 0.560 AC: 622502 AN: 1111240

Other (OTH) AF: 0.547 AC: 33011 AN: 60328

GnomAD4 genome AF: 0.533 AC: 80997 AN: 152050 Hom.: 21908 Cov.: 32 AF XY: 0.526 AC XY: 39054 AN XY: 74302

African (AFR) AF: 0.532 AC: 22053 AN: 41454

American (AMR) AF: 0.564 AC: 8614 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2192 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1483 AN: 5162

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4814

European-Finnish (FIN) AF: 0.449 AC: 4741 AN: 10568

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37880 AN: 67982

Other (OTH) AF: 0.583 AC: 1234 AN: 2116

Alfa AF: 0.548 Hom.: 104096

Bravo AF: 0.544

TwinsUK AF: 0.559 AC: 2071

ALSPAC AF: 0.560 AC: 2158

ESP6500AA AF: 0.553 AC: 2437

ESP6500EA AF: 0.571 AC: 4907

ExAC AF: 0.515 AC: 62550

Asia WGS AF: 0.433 AC: 1509 AN: 3478

EpiCase AF: 0.561

EpiControl AF: 0.573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.016
DANN	Benign	0.044
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.088	T
MetaRNN	Benign	0.0000095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.19
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.026
MPC		0.071
ClinPred		0.00030	T
GERP RS		-3.1
Varity_R		0.020
gMVP		0.13
Mutation Taster		=98/2	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: rs12919; hg19: chr7-156762248; COSMIC: COSV51983597; COSMIC: COSV51983597;