chr3-58569736-C-T

Variant names:

• chr3-58569736-C-T
• rs771660928
• NM_001076778.3:c.125G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001076778.3(FAM107A):​c.125G>A​(p.Arg42Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: FAM107A NM_001076778.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.895
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2373651).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076778.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM107A	NM_001076778.3	MANE Select	c.125G>A	p.Arg42Gln	missense	Exon 2 of 4	NP_001070246.1	O95990-1
	FAM107A	NM_001282714.2		c.218G>A	p.Arg73Gln	missense	Exon 3 of 5	NP_001269643.1	O95990-4
	FAM107A	NM_001282713.2		c.209G>A	p.Arg70Gln	missense	Exon 2 of 4	NP_001269642.1	O95990-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM107A	ENST00000360997.7	TSL:1 MANE Select	c.125G>A	p.Arg42Gln	missense	Exon 2 of 4	ENSP00000354270.2	O95990-1
	FAM107A	ENST00000447756.2	TSL:1	c.209G>A	p.Arg70Gln	missense	Exon 2 of 4	ENSP00000400858.2	O95990-3
	FAM107A	ENST00000394481.5	TSL:1	c.125G>A	p.Arg42Gln	missense	Exon 3 of 5	ENSP00000377991.1	O95990-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461780 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111964

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.0000242 AC: 1 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.24	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.90
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Benign	0.079	T
Sift4G	Benign	0.14	T
Polyphen		0.90	P
Vest4		0.33
MutPred		0.58		Loss of MoRF binding (P = 0.0127)
MVP		0.73
MPC		0.22
ClinPred		0.81	D
GERP RS		3.6
Varity_R		0.086
gMVP		0.065
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs771660928; hg19: chr3-58555463; COSMIC: COSV62981036; COSMIC: COSV62981036;