chr10-122912813-G-T

Position:

• chr10-122912813-G-T

Variant summary

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

The NM_001029888.3(FAM24A):​c.177G>T​(p.Lys59Asn) 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: -0.0400

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=0.15000924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM24A	NM_001029888.3	c.177G>T	p.Lys59Asn	missense_variant	3/3	ENST00000368894.2	NP_001025059.1
FAM24A	XM_017015638.2	c.177G>T	p.Lys59Asn	missense_variant	3/3		XP_016871127.1
FAM24A	XM_017015639.2	c.177G>T	p.Lys59Asn	missense_variant	3/3		XP_016871128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM24A	ENST00000368894.2	c.177G>T	p.Lys59Asn	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

Nov 10, 2022

The c.177G>T (p.K59N) 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 177, causing the lysine (K) at amino acid position 59 to be replaced by an asparagine (N). 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	0.32
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.8
DANN	Benign	0.85
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.037
Sift	Benign	0.062	T
Sift4G	Uncertain	0.035	D
Polyphen		0.94	P
Vest4		0.18
MutPred		0.34		Loss of methylation at K59 (P = 0.0022);
MVP		0.040
MPC		0.12
ClinPred		0.36	T
GERP RS		0.31
Varity_R		0.14
gMVP		0.040

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-124672329;