Genetic Variant FAM168A:p.Gln223Arg (chr11-73407571-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015159.3(FAM168A):c.668A>G(p.Gln223Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,658 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAM168A
NM_015159.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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:):

ENSG00000256448 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25787047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM168A	NM_015159.3 link	c.668A>G	p.Gln223Arg	missense_variant	Exon 7 of 8	ENST00000356467.5	NP_055974.1	Q92567-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM168A	ENST00000356467.5 link	c.668A>G	p.Gln223Arg	missense_variant	Exon 7 of 8	1	NM_015159.3	ENSP00000348852.4		Q92567-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242574

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131968

show subpopulations

Gnomad AFR exome

AF:

0.0000667

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000137

AC:

AN:

1455658

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.668A>G (p.Q223R) alteration is located in exon 7 (coding exon 6) of the FAM168A gene. This alteration results from a A to G substitution at nucleotide position 668, causing the glutamine (Q) at amino acid position 223 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Benign

0.76

DEOGEN2

Benign

0.083

T;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.099

Sift

Benign

0.080

T;D;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.70

MVP

0.12

MPC

1.1

ClinPred

0.25

GERP RS

2.0

Varity_R

0.20

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over