6-70528402-A-G

Variant names:

• chr6-70528402-A-G
• rs2747701
• NM_001162529.3:c.3725A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.35 (11506 hom., cov: 32)
  • Exomes 𝑓: 0.46 (160508 hom.)
• Consequence: FAM135A NM_001162529.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.19
• Publications: 35 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162529.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135A	NM_001162529.3	MANE Select	c.3725A>G	p.Asp1242Gly	missense	Exon 16 of 22	NP_001156001.1
	FAM135A	NM_001330996.3		c.3803A>G	p.Asp1268Gly	missense	Exon 16 of 22	NP_001317925.1
	FAM135A	NM_001330999.3		c.3803A>G	p.Asp1268Gly	missense	Exon 17 of 23	NP_001317928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135A	ENST00000418814.7	TSL:5 MANE Select	c.3725A>G	p.Asp1242Gly	missense	Exon 16 of 22	ENSP00000410768.2
	FAM135A	ENST00000370479.7	TSL:1	c.3725A>G	p.Asp1242Gly	missense	Exon 14 of 20	ENSP00000359510.4
	FAM135A	ENST00000361499.7	TSL:1	c.3137A>G	p.Asp1046Gly	missense	Exon 16 of 22	ENSP00000354913.3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52893 AN: 151890 Hom.: 11512 Cov.: 32

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

GnomAD2 exomes AF: 0.413 AC: 103450 AN: 250500 AF XY: 0.430

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 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.: 39 AF XY: 0.464 AC XY: 336863 AN XY: 726444

African (AFR) AF: 0.0721 AC: 2412 AN: 33460

American (AMR) AF: 0.252 AC: 11218 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 12211 AN: 26072

East Asian (EAS) AF: 0.556 AC: 22055 AN: 39652

South Asian (SAS) AF: 0.477 AC: 41012 AN: 85972

European-Finnish (FIN) AF: 0.418 AC: 22311 AN: 53376

Middle Eastern (MID) AF: 0.450 AC: 2592 AN: 5760

European-Non Finnish (NFE) AF: 0.480 AC: 533662 AN: 1111212

Other (OTH) AF: 0.444 AC: 26773 AN: 60314

GnomAD4 genome AF: 0.348 AC: 52882 AN: 152008 Hom.: 11506 Cov.: 32 AF XY: 0.347 AC XY: 25807 AN XY: 74280

African (AFR) AF: 0.0861 AC: 3574 AN: 41486

American (AMR) AF: 0.309 AC: 4718 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2735 AN: 5154

South Asian (SAS) AF: 0.482 AC: 2326 AN: 4822

European-Finnish (FIN) AF: 0.407 AC: 4303 AN: 10572

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32194 AN: 67932

Other (OTH) AF: 0.368 AC: 777 AN: 2110

Alfa AF: 0.437 Hom.: 53267

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.054
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.00017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.2
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.067	B
Vest4		0.15
MPC		0.25
ClinPred		0.049	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2747701; hg19: chr6-71238105; COSMIC: COSV52047515; COSMIC: COSV52047515;