16-16232671-T-G

Variant names:

• chr16-16232671-T-G
• NM_001004067.4:c.5T>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001004067.4(NOMO3):​c.5T>G​(p.Leu2Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOMO3 NM_001004067.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12

Genes affected

NOMO3 (HGNC:25242): (NODAL modulator 3) This gene encodes a protein originally thought to be related to the collagenase gene family. This gene is one of three highly similar genes in a duplicated region on the short arm of chromosome 16. These three genes encode closely related proteins that may have the same function. The protein encoded by one of these genes has been identified as part of a protein complex that participates in the Nodal signaling pathway during vertebrate development. Mutations in ABCC6, which is located nearby, rather than mutations in this gene are associated with pseudoxanthoma elasticum. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.109576315).
• BP6: Variant 16-16232671-T-G is Benign according to our data. Variant chr16-16232671-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2373593.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOMO3	NM_001004067.4	c.5T>G	p.Leu2Arg	missense_variant	Exon 1 of 31	ENST00000399336.9	NP_001004067.1
NOMO3	XM_005255318.2	c.5T>G	p.Leu2Arg	missense_variant	Exon 1 of 32		XP_005255375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOMO3	ENST00000399336.9	c.5T>G	p.Leu2Arg	missense_variant	Exon 1 of 31	1	NM_001004067.4	ENSP00000382274.4

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000149 AC: 1 AN: 671572 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 323924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 13, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.56
DEOGEN2	Benign	0.0040	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.034
Sift	Benign	0.29	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.30		Gain of methylation at L2 (P = 0.0126);Gain of methylation at L2 (P = 0.0126);
MVP		0.16
ClinPred		0.10	T
GERP RS		-0.73
Varity_R		0.051
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-16326528;