Variant chr22-42411592-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145912.8(NFAM1):c.266G>A(p.Gly89Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NFAM1
NM_145912.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.616

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38162154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NFAM1	NM_145912.8 linkuse as main transcript	c.266G>A	p.Gly89Glu	missense_variant	2/6	ENST00000329021.10
NFAM1	NM_001371362.1 linkuse as main transcript	c.110G>A	p.Gly37Glu	missense_variant	4/8
NFAM1	NM_001318323.3 linkuse as main transcript	c.266G>A	p.Gly89Glu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAM1	ENST00000329021.10 linkuse as main transcript	c.266G>A	p.Gly89Glu	missense_variant	2/6	1	NM_145912.8	P1
NFAM1	ENST00000355469.4 linkuse as main transcript	n.271G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.266G>A (p.G89E) alteration is located in exon 2 (coding exon 2) of the NFAM1 gene. This alteration results from a G to A substitution at nucleotide position 266, causing the glycine (G) at amino acid position 89 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.59

M_CAP

Benign

0.029

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.92

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.066

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.43

MutPred

0.24

Gain of disorder (P = 0.0933);

MVP

0.58

MPC

0.40

ClinPred

0.84

GERP RS

4.1

Varity_R

0.23

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over