Variant 22-42409438-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145912.8(NFAM1):c.561C>G(p.Asn187Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,471,670 control chromosomes in the GnomAD database, including 381 homozygotes. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.029 ( 216 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 165 hom. )

Consequence

NFAM1
NM_145912.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

NFAM1 (HGNC:29872): (NFAT activating protein with ITAM motif 1) The protein encoded by this gene is a type I membrane receptor that activates cytokine gene promoters such as the IL-13 and TNF-alpha promoters. The encoded protein contains an immunoreceptor tyrosine-based activation motif (ITAM) and is thought to regulate the signaling and development of B-cells. [provided by RefSeq, Jul 2008]

NFAM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002044052).

BP6

Variant 22-42409438-G-C is Benign according to our data. Variant chr22-42409438-G-C is described in ClinVar as [Benign]. Clinvar id is 777728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NFAM1	NM_145912.8 linkuse as main transcript	c.561C>G	p.Asn187Lys	missense_variant	3/6	ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1 linkuse as main transcript	c.405C>G	p.Asn135Lys	missense_variant	5/8		NP_001358291.1
NFAM1	NM_001318323.3 linkuse as main transcript	c.451+1969C>G		intron_variant			NP_001305252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10 linkuse as main transcript	c.561C>G	p.Asn187Lys	missense_variant	3/6	1	NM_145912.8	ENSP00000333680	P1

Frequencies

GnomAD3 genomes

AF:

0.0289

AC:

4401

AN:

152192

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00739

AC:

1263

AN:

171004

Hom.:

AF XY:

0.00504

AC XY:

468

AN XY:

92922

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.00265

AC:

3501

AN:

1319360

Hom.:

165

Cov.:

AF XY:

0.00230

AC XY:

1501

AN XY:

652806

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000497

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.00586

GnomAD4 genome

AF:

0.0290

AC:

4412

AN:

152310

Hom.:

216

Cov.:

AF XY:

0.0281

AC XY:

2092

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00514

Hom.:

Bravo

AF:

0.0320

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.102

AC:

450

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00885

AC:

1074

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.060

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

4.2

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.14

MutPred

0.23

Gain of methylation at N187 (P = 0.0108);

MVP

0.055

MPC

0.064

ClinPred

0.0030

GERP RS

4.8

Varity_R

0.051

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over