Genetic Variant FRMD3:c.253-65A>G (chr9-83373020-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_174938.6(FRMD3):c.253-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,303,680 control chromosomes in the GnomAD database, including 99,006 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 0.44 ( 15220 hom., cov: 31)

Exomes 𝑓: 0.37 ( 83786 hom. )

Consequence

FRMD3
NM_174938.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

8 publications found

Variant links:

Genes affected

FRMD3 (HGNC:24125): (FERM domain containing 3) The protein encoded by this gene is a single pass membrane protein primarily found in ovaries. A similar protein in erythrocytes helps determine the shape of red blood cells, but the function of the encoded protein has not been determined. There is some evidence that this is a tumor suppressor gene, and there is also evidence linking defects in this gene to susceptibility to diabetic nephropathy in type 1 diabetes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

FRMD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174938.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FRMD3	NM_174938.6	MANE Select	c.253-65A>G	intron	N/A	NP_777598.3
FRMD3	NM_001244959.2		c.253-65A>G	intron	N/A	NP_001231888.1
FRMD3	NM_001244960.2		c.121-65A>G	intron	N/A	NP_001231889.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.253-65A>G	intron	N/A	ENSP00000303508.3
FRMD3	ENST00000621208.4	TSL:1	c.121-65A>G	intron	N/A	ENSP00000484839.1
FRMD3	ENST00000376438.5	TSL:2	c.253-65A>G	intron	N/A	ENSP00000365621.1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66342

AN:

151010

Hom.:

15183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.397

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.374

AC:

431362

AN:

1152578

Hom.:

83786

AF XY:

0.375

AC XY:

220784

AN XY:

588294

show subpopulations

African (AFR)

AF:

0.568

AC:

15122

AN:

26620

American (AMR)

AF:

0.470

AC:

20275

AN:

43094

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

8850

AN:

24068

East Asian (EAS)

AF:

0.406

AC:

15541

AN:

38264

South Asian (SAS)

AF:

0.373

AC:

29583

AN:

79218

European-Finnish (FIN)

AF:

0.459

AC:

21045

AN:

45800

Middle Eastern (MID)

AF:

0.369

AC:

1890

AN:

5128

European-Non Finnish (NFE)

AF:

0.357

AC:

299660

AN:

840242

Other (OTH)

AF:

0.387

AC:

19396

AN:

50144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13188

26376

39563

52751

65939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8310

16620

24930

33240

41550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.440

AC:

66434

AN:

151102

Hom.:

15220

Cov.:

AF XY:

0.441

AC XY:

32528

AN XY:

73768

show subpopulations

African (AFR)

AF:

0.570

AC:

23486

AN:

41208

American (AMR)

AF:

0.403

AC:

6130

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1232

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2246

AN:

5148

South Asian (SAS)

AF:

0.365

AC:

1745

AN:

4782

European-Finnish (FIN)

AF:

0.469

AC:

4785

AN:

10210

Middle Eastern (MID)

AF:

0.385

AC:

110

AN:

286

European-Non Finnish (NFE)

AF:

0.378

AC:

25618

AN:

67794

Other (OTH)

AF:

0.436

AC:

914

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.389

Hom.:

19185

Bravo

AF:

0.443

Asia WGS

AF:

0.375

AC:

1307

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.3

(source)

DANN

Benign

0.32

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over