chr10-122912800-A-T

Position:

• chr10-122912800-A-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.164A>T​(p.His55Leu) 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. 15/20 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: -3.00

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=0.08533418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM24A	NM_001029888.3	c.164A>T	p.His55Leu	missense_variant	3/3	ENST00000368894.2	NP_001025059.1
FAM24A	XM_017015638.2	c.164A>T	p.His55Leu	missense_variant	3/3		XP_016871127.1
FAM24A	XM_017015639.2	c.164A>T	p.His55Leu	missense_variant	3/3		XP_016871128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM24A	ENST00000368894.2	c.164A>T	p.His55Leu	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

Feb 05, 2024

The c.164A>T (p.H55L) alteration is located in exon 3 (coding exon 2) of the FAM24A gene. This alteration results from a A to T substitution at nucleotide position 164, causing the histidine (H) at amino acid position 55 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.017
DANN	Benign	0.82
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Benign	0.46	T
Sift4G	Benign	0.10	T
Polyphen		0.35	B
Vest4		0.24
MutPred		0.21		Gain of sheet (P = 0.039);
MVP		0.067
MPC		0.22
ClinPred		0.34	T
GERP RS		-1.8
Varity_R		0.10
gMVP		0.016

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: chr10-124672316;