Genetic Variant NM_015159.3:c.547G>C (chr11-73409535-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015159.3(FAM168A):c.547G>C(p.Gly183Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G183S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

FAM168A
NM_015159.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.65

Publications

0 publications found

Variant links:

Genes affected

FAM168A (HGNC:28999): (family with sequence similarity 168 member A) Involved in positive regulation of base-excision repair. [provided by Alliance of Genome Resources, Apr 2022]

FAM168A links:

ENSG00000256448 (HGNC:58441):

ENSG00000256448 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015159.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM168A	NM_015159.3	MANE Select	c.547G>C	p.Gly183Arg	missense	Exon 6 of 8	NP_055974.1	Q92567-2
FAM168A	NM_001286050.2		c.574G>C	p.Gly192Arg	missense	Exon 7 of 9	NP_001272979.1	Q92567-1
FAM168A	NM_001286051.2		c.278-1892G>C		intron	N/A	NP_001272980.1	Q92567-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM168A	ENST00000356467.5	TSL:1 MANE Select	c.547G>C	p.Gly183Arg	missense	Exon 6 of 8	ENSP00000348852.4	Q92567-2
FAM168A	ENST00000064778.8	TSL:1	c.574G>C	p.Gly192Arg	missense	Exon 7 of 9	ENSP00000064778.4	Q92567-1
FAM168A	ENST00000450446.6	TSL:1	c.278-1892G>C		intron	N/A	ENSP00000390501.2	Q92567-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.2

PhyloP100

4.7

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Benign

0.075

Polyphen

1.0

Vest4

0.92

MutPred

0.54

Gain of MoRF binding (P = 0.0065)

MVP

0.57

MPC

0.73

ClinPred

0.99

GERP RS

5.6

Varity_R

0.73

gMVP

0.77

Mutation Taster

=61/39

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