10-122850511-G-C

Position:

• chr10-122850511-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152644.3(FAM24B):​c.5C>G​(p.Pro2Arg) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM24B NM_152644.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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-CUZD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071091294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM24B	NM_152644.3	c.5C>G	p.Pro2Arg	missense_variant	3/4	ENST00000368898.8
FAM24B-CUZD1	NR_037915.1	n.300-4291C>G		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1	c.5C>G	p.Pro2Arg	missense_variant	3/4
FAM24B	NR_037911.1	n.300-1072C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM24B	ENST00000368898.8	c.5C>G	p.Pro2Arg	missense_variant	3/4	1	NM_152644.3	P1
FAM24B	ENST00000368896.1	c.5C>G	p.Pro2Arg	missense_variant	3/4	2		P1
FAM24B	ENST00000462859.5	n.300-1072C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.81
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.043
Sift	Benign	0.075	T;T
Sift4G	Uncertain	0.040	D;D
Polyphen		0.0	B;B
Vest4		0.038
MutPred		0.23		Gain of methylation at P2 (P = 0.0248);Gain of methylation at P2 (P = 0.0248);
MVP		0.040
MPC		0.27
ClinPred		0.046	T
GERP RS		3.0
Varity_R		0.016
gMVP		0.057

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

Other links and lift over

dbSNP: rs1891110; hg19: chr10-124610027;