10-122912803-A-G

Variant names:

• chr10-122912803-A-G
• rs1206440016
• NM_001029888.3:c.167A>G

Variant summary

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

The NM_001029888.3(FAM24A):​c.167A>G​(p.Asn56Ser) 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. 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: -0.445

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0724442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM24A	NM_001029888.3	c.167A>G	p.Asn56Ser	missense_variant	Exon 3 of 3	ENST00000368894.2	NP_001025059.1
FAM24A	XM_017015638.2	c.167A>G	p.Asn56Ser	missense_variant	Exon 3 of 3		XP_016871127.1
FAM24A	XM_017015639.2	c.167A>G	p.Asn56Ser	missense_variant	Exon 3 of 3		XP_016871128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM24A	ENST00000368894.2	c.167A>G	p.Asn56Ser	missense_variant	Exon 3 of 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

May 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167A>G (p.N56S) alteration is located in exon 3 (coding exon 2) of the FAM24A gene. This alteration results from a A to G substitution at nucleotide position 167, causing the asparagine (N) at amino acid position 56 to be replaced by a serine (S). 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	0.084
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.37
DANN	Benign	0.60
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.0060
Sift	Benign	0.24	T
Sift4G	Benign	0.30	T
Polyphen		0.0050	B
Vest4		0.074
MutPred		0.23		Gain of disorder (P = 0.0794);
MVP		0.014
MPC		0.086
ClinPred		0.050	T
GERP RS		-1.8
Varity_R		0.037
gMVP		0.0085

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1206440016; hg19: chr10-124672319;