rs747766088

Variant names:

• chr10-122849359-T-C
• rs747766088
• NM_152644.3:c.173A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 14/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.415
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048395574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152644.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B	NM_152644.3	MANE Select	c.173A>G	p.Lys58Arg	missense	Exon 4 of 4	NP_689857.2	Q8N5W8
	FAM24B	NM_001204364.1		c.173A>G	p.Lys58Arg	missense	Exon 4 of 4	NP_001191293.1	Q8N5W8
	FAM24B	NR_037911.1		n.380A>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B	ENST00000368898.8	TSL:1 MANE Select	c.173A>G	p.Lys58Arg	missense	Exon 4 of 4	ENSP00000357894.3	Q8N5W8
	ENSG00000286088	ENST00000368904.6	TSL:1	n.-377-3139A>G		intron	N/A	ENSP00000357900.2	A0A499FIG0
	FAM24B	ENST00000368896.1	TSL:2	c.173A>G	p.Lys58Arg	missense	Exon 4 of 4	ENSP00000357892.1	Q8N5W8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250548 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461242 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 726890

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111712

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.41
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.012
Sift	Benign	0.17	T
Sift4G	Benign	0.22	T
Polyphen		0.021	B
Vest4		0.097
MutPred		0.27		Loss of ubiquitination at K58 (P = 0.0107)
MVP		0.055
MPC		0.50
ClinPred		0.14	T
GERP RS		-1.4
Varity_R		0.026
gMVP		0.026
Mutation Taster		=298/2	polymorphism

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

Other links and lift over

dbSNP: rs747766088; hg19: chr10-124608875;