NM_152644.3:c.13G>T

Variant names:

• chr10-122850503-C-A
• rs141194908
• NM_152644.3:c.13G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152644.3(FAM24B):​c.13G>T​(p.Ala5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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. A5T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM24B NM_152644.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.13G>T	p.Ala5Ser	missense	Exon 3 of 4	NP_689857.2	Q8N5W8
	FAM24B	NM_001204364.1		c.13G>T	p.Ala5Ser	missense	Exon 3 of 4	NP_001191293.1	Q8N5W8
	FAM24B	NR_037911.1		n.300-1064G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B	ENST00000368898.8	TSL:1 MANE Select	c.13G>T	p.Ala5Ser	missense	Exon 3 of 4	ENSP00000357894.3	Q8N5W8
	ENSG00000286088	ENST00000368904.6	TSL:1	n.-377-4283G>T		intron	N/A	ENSP00000357900.2	A0A499FIG0
	FAM24B	ENST00000368896.1	TSL:2	c.13G>T	p.Ala5Ser	missense	Exon 3 of 4	ENSP00000357892.1	Q8N5W8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460892 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726840

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111108

Other (OTH) AF: 0.0000331 AC: 2 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.2
DANN	Benign	0.87
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.033
Sift	Benign	0.18	T
Sift4G	Uncertain	0.055	T
Polyphen		0.87	P
Vest4		0.082
MutPred		0.36		Gain of glycosylation at A5 (P = 7e-04)
MVP		0.095
MPC		0.23
ClinPred		0.21	T
GERP RS		0.97
Varity_R		0.028
gMVP		0.074
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: 47

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141194908; hg19: chr10-124610019;