2-100470489-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1 BP6_Moderate BA1

The NM_001011717.1(NMS):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00329 in 1,613,340 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (169 hom.)
• Consequence: NMS NM_001011717.1 start_lost
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.21

Genes affected

NMS (HGNC:32203): (neuromedin S) This gene encodes a member of the neuromedin family of neuropeptides. The encoded preproprotein is proteolytically processed to generate a biologically active neuropeptide that plays a role in the regulation of circadian rhythm, anorexigenic action, antidiuretic action, cardiovascular function and stimulation of oxytocin and vasopressin release. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BP6: Variant 2-100470489-A-G is Benign according to our data. Variant chr2-100470489-A-G is described in ClinVar as [Benign]. Clinvar id is 782803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMS	NM_001011717.1	c.1A>G	p.Met1?	start_lost	1/10	ENST00000376865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMS	ENST00000376865.1	c.1A>G	p.Met1?	start_lost	1/10	1	NM_001011717.1	P1

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 660 AN: 152134 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00840 AC: 2111 AN: 251410 Hom.: 92 AF XY: 0.00798 AC XY: 1084 AN XY: 135876

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.000694

Gnomad EAS exome AF: 0.0955

Gnomad SAS exome AF: 0.00252

Gnomad FIN exome AF: 0.00635

Gnomad NFE exome AF: 0.000791

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00318 AC: 4641 AN: 1461088 Hom.: 169 Cov.: 30 AF XY: 0.00318 AC XY: 2313 AN XY: 726926

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.0831

Gnomad4 SAS exome AF: 0.00339

Gnomad4 FIN exome AF: 0.00495

Gnomad4 NFE exome AF: 0.000374

Gnomad4 OTH exome AF: 0.00552

GnomAD4 genome AF: 0.00433 AC: 659 AN: 152252 Hom.: 28 Cov.: 32 AF XY: 0.00519 AC XY: 386 AN XY: 74432

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.0919

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00427

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00836 AC: 1015

Asia WGS AF: 0.0380 AC: 130 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.090
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	0.072
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.96	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.77	P
Vest4		0.73
MVP		0.38
ClinPred		0.13	T
GERP RS		4.3
Varity_R		0.94
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs59029020; hg19: chr2-101086951; COSMIC: COSV65259265;