Genetic Variant NM_001013647.2:c.1180A>G (chr22-38605295-T-C) – 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_001013647.2(FAM227A):c.1180A>G(p.Ile394Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,551,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

FAM227A
NM_001013647.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.800

Publications

0 publications found

Variant links:

Genes affected

FAM227A (HGNC:44197): (family with sequence similarity 227 member A)

FAM227A links:

Genome browser will be placed here

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=0.09183973).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013647.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM227A	NM_001013647.2	MANE Select	c.1180A>G	p.Ile394Val	missense	Exon 13 of 17	NP_001013669.1	F5H4B4-1
FAM227A	NM_001384270.1		c.913A>G	p.Ile305Val	missense	Exon 13 of 17	NP_001371199.1
FAM227A	NM_001291030.2		c.901A>G	p.Ile301Val	missense	Exon 13 of 17	NP_001277959.1	F5H4B4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM227A	ENST00000535113.7	TSL:5 MANE Select	c.1180A>G	p.Ile394Val	missense	Exon 13 of 17	ENSP00000445093.1	F5H4B4-1
FAM227A	ENST00000355830.11	TSL:5	c.1180A>G	p.Ile394Val	missense	Exon 13 of 19	ENSP00000348086.7	A0A0A0MRD0
FAM227A	ENST00000540952.6	TSL:5	c.1180A>G	p.Ile394Val	missense	Exon 13 of 17	ENSP00000493504.1	A0A2R8YCE3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000630

AC:

AN:

158834

AF XY:

0.0000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000786

AC:

AN:

1399008

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690074

show subpopulations

African (AFR)

AF:

0.0000950

AC:

AN:

31574

American (AMR)

AF:

0.0000280

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25172

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00000556

AC:

AN:

1078206

Other (OTH)

AF:

0.0000172

AC:

AN:

58162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

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

AF:

0.0000197

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000681

Hom.:

Bravo

AF:

0.0000113

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

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.57

M_CAP

Benign

0.0024

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

0.80

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.37

REVEL

Benign

0.051

Sift

Benign

0.36

Sift4G

Benign

0.17

Polyphen

0.34

Vest4

0.077

MutPred

0.20

Loss of loop (P = 0.0022)

MVP

0.030

ClinPred

0.13

GERP RS

1.2

Varity_R

0.036

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over