dbSNP rs4877253: FRMD3:c.374+144T>C (chr9-83349535-A-G) – 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.374+144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 573,820 control chromosomes in the GnomAD database, including 31,033 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 0.31 ( 7771 hom., cov: 32)

Exomes 𝑓: 0.32 ( 23262 hom. )

Consequence

FRMD3
NM_174938.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

Publications

2 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=-0.5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 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.374+144T>C	intron	N/A	NP_777598.3
FRMD3	NM_001244959.2		c.374+144T>C	intron	N/A	NP_001231888.1
FRMD3	NM_001244960.2		c.242+144T>C	intron	N/A	NP_001231889.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.374+144T>C	intron	N/A	ENSP00000303508.3
FRMD3	ENST00000621208.4	TSL:1	c.242+144T>C	intron	N/A	ENSP00000484839.1
FRMD3	ENST00000376438.5	TSL:2	c.374+144T>C	intron	N/A	ENSP00000365621.1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47410

AN:

151984

Hom.:

7767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.0806

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.322

AC:

135676

AN:

421718

Hom.:

23262

AF XY:

0.319

AC XY:

71521

AN XY:

224070

show subpopulations

African (AFR)

AF:

0.265

AC:

3097

AN:

11670

American (AMR)

AF:

0.352

AC:

6074

AN:

17242

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

3430

AN:

12958

East Asian (EAS)

AF:

0.117

AC:

3487

AN:

29810

South Asian (SAS)

AF:

0.255

AC:

9538

AN:

37450

European-Finnish (FIN)

AF:

0.389

AC:

11463

AN:

29458

Middle Eastern (MID)

AF:

0.319

AC:

1109

AN:

3480

European-Non Finnish (NFE)

AF:

0.352

AC:

89731

AN:

255028

Other (OTH)

AF:

0.315

AC:

7747

AN:

24622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

4282

8565

12847

17130

21412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.312

AC:

47431

AN:

152102

Hom.:

7771

Cov.:

AF XY:

0.310

AC XY:

23054

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.264

AC:

10956

AN:

41482

American (AMR)

AF:

0.344

AC:

5257

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

910

AN:

3472

East Asian (EAS)

AF:

0.0808

AC:

419

AN:

5188

South Asian (SAS)

AF:

0.247

AC:

1192

AN:

4820

European-Finnish (FIN)

AF:

0.376

AC:

3973

AN:

10566

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.349

AC:

23716

AN:

67992

Other (OTH)

AF:

0.291

AC:

612

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1664

3328

4991

6655

8319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.327

Hom.:

5001

Bravo

AF:

0.305

Asia WGS

AF:

0.218

AC:

758

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

2.3

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