Variant 6-70528402-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001162529.3(FAM135A):c.3725A>G(p.Asp1242Gly) variant causes a missense change. The variant allele was found at a frequency of 0.451 in 1,612,320 control chromosomes in the GnomAD database, including 172,014 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.35 ( 11506 hom., cov: 32)

Exomes 𝑓: 0.46 ( 160508 hom. )

Consequence

FAM135A
NM_001162529.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.19

Variant links:

Genes affected

FAM135A (HGNC:21084): (family with sequence similarity 135 member A) Predicted to be involved in cellular lipid metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

FAM135A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6963482E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM135A	NM_001162529.3 linkuse as main transcript	c.3725A>G	p.Asp1242Gly	missense_variant	16/22	ENST00000418814.7	NP_001156001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM135A	ENST00000418814.7 linkuse as main transcript	c.3725A>G	p.Asp1242Gly	missense_variant	16/22	5	NM_001162529.3	ENSP00000410768	A1	Q9P2D6-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52893

AN:

151890

Hom.:

11512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0864

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.413

AC:

103450

AN:

250500

Hom.:

23346

AF XY:

0.430

AC XY:

58256

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.0753

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.531

Gnomad SAS exome

AF:

0.474

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.462

AC:

674246

AN:

1460312

Hom.:

160508

Cov.:

AF XY:

0.464

AC XY:

336863

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.0721

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.556

Gnomad4 SAS exome

AF:

0.477

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.480

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.348

AC:

52882

AN:

152008

Hom.:

11506

Cov.:

AF XY:

0.347

AC XY:

25807

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0861

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.531

Gnomad4 SAS

AF:

0.482

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.458

Hom.:

40671

Bravo

AF:

0.329

TwinsUK

AF:

0.488

AC:

1809

ALSPAC

AF:

0.481

AC:

1852

ESP6500AA

AF:

0.0865

AC:

381

ESP6500EA

AF:

0.481

AC:

4138

ExAC

AF:

0.415

AC:

50351

Asia WGS

AF:

0.398

AC:

1383

AN:

3478

EpiCase

AF:

0.486

EpiControl

AF:

0.485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T;.;.;T;.

Eigen

Benign

-0.099

Eigen_PC

Benign

-0.054

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

.;T;T;T;T;T

MetaRNN

Benign

0.00017

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.;.;M;M

MutationTaster

Benign

0.0000065

P;P;P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.3

D;D;D;D;.;D

REVEL

Benign

0.15

Sift

Uncertain

0.018

D;T;D;D;.;D

Sift4G

Uncertain

0.0050

D;T;D;D;D;D

Polyphen

0.067

B;B;B;B;B;B

Vest4

0.15

MPC

0.25

ClinPred

0.049

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over