3-58566658-G-C

Position:

• chr3-58566658-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001076778.3(FAM107A):​c.365C>G​(p.Pro122Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM107A NM_001076778.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.48

Genes affected

FAM107A (HGNC:30827): (family with sequence similarity 107 member A) Predicted to enable actin binding activity. Involved in several processes, including negative regulation of G1/S transition of mitotic cell cycle; negative regulation of focal adhesion assembly; and regulation of cytoskeleton organization. Located in several cellular components, including focal adhesion; ruffle membrane; and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984079 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM107A	NM_001076778.3	c.365C>G	p.Pro122Arg	missense_variant	4/4	ENST00000360997.7
LOC107984079	XR_001740724.2	n.944-6089G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM107A	ENST00000360997.7	c.365C>G	p.Pro122Arg	missense_variant	4/4	1	NM_001076778.3	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 27, 2023

The c.365C>G (p.P122R) alteration is located in exon 5 (coding exon 3) of the FAM107A gene. This alteration results from a C to G substitution at nucleotide position 365, causing the proline (P) at amino acid position 122 to be replaced by an arginine (R). 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	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;T;.;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;.;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Uncertain	-0.074	T
MutationAssessor	Pathogenic	2.9	M;M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-7.8	D;D;.;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0020	D;D;.;D;D
Sift4G	Uncertain	0.0030	D;D;.;D;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.88
MutPred		0.69		Gain of MoRF binding (P = 0.0064);Gain of MoRF binding (P = 0.0064);Gain of MoRF binding (P = 0.0064);.;.;
MVP		0.79
MPC		0.57
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.76
gMVP		0.33

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: chr3-58552385;