Variant chr10-122849359-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152644.3(FAM24B):c.173A>G(p.Lys58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FAM24B
NM_152644.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.415

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048395574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM24B	NM_152644.3 linkuse as main transcript	c.173A>G	p.Lys58Arg	missense_variant	4/4	ENST00000368898.8	NP_689857.2
FAM24B-CUZD1	NR_037915.1 linkuse as main transcript	n.300-3139A>G		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1 linkuse as main transcript	c.173A>G	p.Lys58Arg	missense_variant	4/4		NP_001191293.1
FAM24B	NR_037911.1 linkuse as main transcript	n.380A>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.173A>G	p.Lys58Arg	missense_variant	4/4	1	NM_152644.3	ENSP00000357894	P1
FAM24B	ENST00000368896.1 linkuse as main transcript	c.173A>G	p.Lys58Arg	missense_variant	4/4	2		ENSP00000357892	P1
FAM24B	ENST00000462859.5 linkuse as main transcript	n.380A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250548

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461242

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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 06, 2022

The c.173A>G (p.K58R) 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 173, causing the lysine (K) at amino acid position 58 to be replaced by an arginine (R). 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

0.089

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.30

.;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.012

Sift

Benign

0.17

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.021

B;B

Vest4

0.097

MutPred

0.27

Loss of ubiquitination at K58 (P = 0.0107);Loss of ubiquitination at K58 (P = 0.0107);

MVP

0.055

MPC

0.50

ClinPred

0.14

GERP RS

-1.4

Varity_R

0.026

gMVP

0.026

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