10-122912926-G-T

Position:

• chr10-122912926-G-T

Variant summary

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

The NM_001029888.3(FAM24A):​c.290G>T​(p.Cys97Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM24A NM_001029888.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56

Genes affected

FAM24A (HGNC:23470): (family with sequence similarity 24 member A) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM24A	NM_001029888.3	c.290G>T	p.Cys97Phe	missense_variant	3/3	ENST00000368894.2	NP_001025059.1
FAM24A	XM_017015638.2	c.290G>T	p.Cys97Phe	missense_variant	3/3		XP_016871127.1
FAM24A	XM_017015639.2	c.290G>T	p.Cys97Phe	missense_variant	3/3		XP_016871128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM24A	ENST00000368894.2	c.290G>T	p.Cys97Phe	missense_variant	3/3	3	NM_001029888.3	ENSP00000357889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.290G>T (p.C97F) alteration is located in exon 3 (coding exon 2) of the FAM24A gene. This alteration results from a G to T substitution at nucleotide position 290, causing the cysteine (C) at amino acid position 97 to be replaced by a phenylalanine (F). 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	0.31
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0054	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-9.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.40		Loss of catalytic residue at P96 (P = 0.0179);
MVP		0.16
MPC		0.65
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.85
gMVP		0.035

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-124672442;