Genetic Variant FAM163A:p.Thr127Arg (chr1-179814065-C-G) – 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_173509.3(FAM163A):c.380C>G(p.Thr127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAM163A
NM_173509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Publications

0 publications found

Variant links:

Genes affected

FAM163A (HGNC:28274): (family with sequence similarity 163 member A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM163A links:

ENSG00000297013 (HGNC:):

ENSG00000297013 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=0.14244834).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173509.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM163A	NM_173509.3	MANE Select	c.380C>G	p.Thr127Arg	missense	Exon 5 of 5	NP_775780.1	Q96GL9
FAM163A	NM_001329712.2		c.380C>G	p.Thr127Arg	missense	Exon 5 of 5	NP_001316641.1	Q96GL9
FAM163A	NM_001329713.2		c.380C>G	p.Thr127Arg	missense	Exon 6 of 6	NP_001316642.1	Q96GL9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM163A	ENST00000341785.5	TSL:1 MANE Select	c.380C>G	p.Thr127Arg	missense	Exon 5 of 5	ENSP00000354891.4	Q96GL9
FAM163A	ENST00000879738.1		c.380C>G	p.Thr127Arg	missense	Exon 5 of 5	ENSP00000549797.1
FAM163A	ENST00000879739.1		c.380C>G	p.Thr127Arg	missense	Exon 5 of 5	ENSP00000549798.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250944

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

6.84e-7

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

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:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111942

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

0.14

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.034

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.61

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

PhyloP100

1.8

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.11

Sift

Benign

0.056

Sift4G

Benign

0.097

Polyphen

0.74

Vest4

0.41

MutPred

0.33

Loss of phosphorylation at T127 (P = 0.029)

MVP

0.23

MPC

0.72

ClinPred

0.66

GERP RS

3.7

Varity_R

0.13

gMVP

0.72

Mutation Taster

=73/27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over