10-122849257-T-C

Variant names:

• chr10-122849257-T-C
• NM_152644.3:c.275A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41849422).

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.275A>G	p.Glu92Gly	missense	Exon 4 of 4	NP_689857.2	Q8N5W8
	FAM24B	NM_001204364.1		c.275A>G	p.Glu92Gly	missense	Exon 4 of 4	NP_001191293.1	Q8N5W8
	FAM24B	NR_037911.1		n.482A>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.275A>G	p.Glu92Gly	missense	Exon 4 of 4	ENSP00000357894.3	Q8N5W8
	ENSG00000286088	ENST00000368904.6	TSL:1	n.-377-3037A>G		intron	N/A	ENSP00000357900.2	A0A499FIG0
	FAM24B	ENST00000368896.1	TSL:2	c.275A>G	p.Glu92Gly	missense	Exon 4 of 4	ENSP00000357892.1	Q8N5W8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1412034 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 696012

African (AFR) AF: 0.00 AC: 0 AN: 31988

American (AMR) AF: 0.00 AC: 0 AN: 39336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24732

East Asian (EAS) AF: 0.00 AC: 0 AN: 37938

South Asian (SAS) AF: 0.00 AC: 0 AN: 79440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082086

Other (OTH) AF: 0.00 AC: 0 AN: 58182

GnomAD4 genome Cov.: 32

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	0.23
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.38	T
PhyloP100		2.9
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.25
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.26		Loss of solvent accessibility (P = 0.0387)
MVP		0.62
MPC		0.99
ClinPred		0.96	D
GERP RS		3.1
Varity_R		0.24
gMVP		0.067
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr10-124608773;