10-122850432-G-C

Variant names:

• chr10-122850432-G-C
• rs141756767
• NM_152644.3:c.84C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152644.3(FAM24B):​c.84C>G​(p.Asn28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: FAM24B NM_152644.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81

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]

ENSG00000286088 (HGNC:):

ACMG classification

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=0.024696052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM24B	NM_152644.3	c.84C>G	p.Asn28Lys	missense_variant	Exon 3 of 4	ENST00000368898.8	NP_689857.2
FAM24B	NM_001204364.1	c.84C>G	p.Asn28Lys	missense_variant	Exon 3 of 4		NP_001191293.1
FAM24B	NR_037911.1	n.300-993C>G		intron_variant	Intron 2 of 2
FAM24B-CUZD1	NR_037915.1	n.300-4212C>G		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM24B	ENST00000368898.8	c.84C>G	p.Asn28Lys	missense_variant	Exon 3 of 4	1	NM_152644.3	ENSP00000357894.3
ENSG00000286088	ENST00000368904.6	n.-377-4212C>G		intron_variant	Intron 1 of 9	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251398 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461296 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726998

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: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.84C>G (p.N28K) alteration is located in exon 3 (coding exon 1) of the FAM24B gene. This alteration results from a C to G substitution at nucleotide position 84, causing the asparagine (N) at amino acid position 28 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0020
DANN	Benign	0.54
DEOGEN2	Benign	0.0039	T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.21	.;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.025	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.017	B;B
Vest4		0.077
MutPred		0.27		Gain of methylation at N28 (P = 0.012);Gain of methylation at N28 (P = 0.012);
MVP		0.10
MPC		0.29
ClinPred		0.063	T
GERP RS		-5.9
Varity_R		0.031
gMVP		0.032

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs141756767; hg19: chr10-124609948;