7-156969554-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138400.2(NOM1):​c.2434G>T​(p.Val812Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019320756).

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>T	p.Val812Leu	missense	Exon 11 of 11	NP_612409.1	Q5C9Z4
	NOM1	NM_001353366.2		c.2437G>T	p.Val813Leu	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>T	p.Val812Leu	missense	Exon 11 of 11	ENSP00000275820.3	Q5C9Z4
	NOM1	ENST00000851672.1		c.2437G>T	p.Val813Leu	missense	Exon 11 of 11	ENSP00000521731.1
	NOM1	ENST00000851673.1		c.2233G>T	p.Val745Leu	missense	Exon 11 of 11	ENSP00000521732.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461400 Hom.: 0 Cov.: 42 AF XY: 0.00000138 AC XY: 1 AN XY: 726968

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111746

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74216

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 104096

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.094
DANN	Benign	0.86
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.11	N
PhyloP100		-0.19
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.17
Sift	Benign	0.60	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.094
MutPred		0.32		Loss of helix (P = 0.028)
MVP		0.061
MPC		0.069
ClinPred		0.036	T
GERP RS		-3.1
Varity_R		0.031
gMVP		0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;