Genetic Variant NM_001076778.3:c.416G>T (chr3-58566607-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001076778.3(FAM107A):c.416G>T(p.Ser139Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S139R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

FAM107A
NM_001076778.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Publications

0 publications found

Variant links:

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]

FAM107A links:

LOC107984079 (HGNC:):

LOC107984079 links:

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ACMG classification

Classification was made for transcript

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=0.11543685).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM107A	NM_001076778.3	MANE Select	c.416G>T	p.Ser139Ile	missense	Exon 4 of 4	NP_001070246.1	O95990-1
FAM107A	NM_001282714.2		c.509G>T	p.Ser170Ile	missense	Exon 5 of 5	NP_001269643.1	O95990-4
FAM107A	NM_001282713.2		c.500G>T	p.Ser167Ile	missense	Exon 4 of 4	NP_001269642.1	O95990-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM107A	ENST00000360997.7	TSL:1 MANE Select	c.416G>T	p.Ser139Ile	missense	Exon 4 of 4	ENSP00000354270.2	O95990-1
FAM107A	ENST00000447756.2	TSL:1	c.500G>T	p.Ser167Ile	missense	Exon 4 of 4	ENSP00000400858.2	O95990-3
FAM107A	ENST00000394481.5	TSL:1	c.416G>T	p.Ser139Ile	missense	Exon 5 of 5	ENSP00000377991.1	O95990-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251276

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461364

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111760

Other (OTH)

AF:

0.0000331

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.81

M_CAP

Benign

0.023

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.6

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.055

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.033

Polyphen

0.72

Vest4

0.073

MutPred

0.25

Loss of phosphorylation at S139 (P = 0.0193)

MVP

0.50

MPC

0.26

ClinPred

0.22

GERP RS

2.2

Varity_R

0.17

gMVP

0.20

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over