Variant 10-122849257-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152644.3(FAM24B):c.275A>G(p.Glu92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM24B
NM_152644.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Variant links:

Genes affected

FAM24B (HGNC:23475): (family with sequence similarity 24 member B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

FAM24B links:

FAM24B-CUZD1 (HGNC:):

FAM24B-CUZD1 links:

Genome browser will be placed here

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=0.41849422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM24B	NM_152644.3 linkuse as main transcript	c.275A>G	p.Glu92Gly	missense_variant	4/4	ENST00000368898.8	NP_689857.2
FAM24B-CUZD1	NR_037915.1 linkuse as main transcript	n.300-3037A>G		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1 linkuse as main transcript	c.275A>G	p.Glu92Gly	missense_variant	4/4		NP_001191293.1
FAM24B	NR_037911.1 linkuse as main transcript	n.482A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FAM24B	ENST00000368898.8 linkuse as main transcript	c.275A>G	p.Glu92Gly	missense_variant	4/4	1	NM_152644.3	ENSP00000357894	P1
FAM24B	ENST00000368896.1 linkuse as main transcript	c.275A>G	p.Glu92Gly	missense_variant	4/4	2		ENSP00000357892	P1
FAM24B	ENST00000462859.5 linkuse as main transcript	n.482A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1412034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696012

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:

0.00

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

Dec 15, 2023

The c.275A>G (p.E92G) alteration is located in exon 4 (coding exon 2) of the FAM24B gene. This alteration results from a A to G substitution at nucleotide position 275, causing the glutamic acid (E) at amino acid position 92 to be replaced by a glycine (G). 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

Benign

0.23

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.50

.;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.38

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.42

MutPred

0.26

Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);

MVP

0.62

MPC

0.99

ClinPred

0.96

GERP RS

3.1

Varity_R

0.24

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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