Variant chr10-122849268-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152644.3(FAM24B):c.264C>G(p.Cys88Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,417,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

FAM24B
NM_152644.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM24B	NM_152644.3 linkuse as main transcript	c.264C>G	p.Cys88Trp	missense_variant	4/4	ENST00000368898.8	NP_689857.2
FAM24B-CUZD1	NR_037915.1 linkuse as main transcript	n.300-3048C>G		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1 linkuse as main transcript	c.264C>G	p.Cys88Trp	missense_variant	4/4		NP_001191293.1
FAM24B	NR_037911.1 linkuse as main transcript	n.471C>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.264C>G	p.Cys88Trp	missense_variant	4/4	1	NM_152644.3	ENSP00000357894	P1
FAM24B	ENST00000368896.1 linkuse as main transcript	c.264C>G	p.Cys88Trp	missense_variant	4/4	2		ENSP00000357892	P1
FAM24B	ENST00000462859.5 linkuse as main transcript	n.471C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000423

AC:

AN:

1417774

Hom.:

Cov.:

AF XY:

0.00000428

AC XY:

AN XY:

700198

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000553

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 26, 2023

The c.264C>G (p.C88W) alteration is located in exon 4 (coding exon 2) of the FAM24B gene. This alteration results from a C to G substitution at nucleotide position 264, causing the cysteine (C) at amino acid position 88 to be replaced by a tryptophan (W). 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

0.42

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

.;T

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.53

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-9.6

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0090

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.90

MutPred

0.51

Gain of solvent accessibility (P = 0.0133);Gain of solvent accessibility (P = 0.0133);

MVP

0.45

MPC

1.1

ClinPred

0.99

GERP RS

2.0

Varity_R

0.34

gMVP

0.063

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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