9-83373020-T-C

Variant names:

• chr9-83373020-T-C
• rs3739657
• NM_174938.6:c.253-65A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 8 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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	A2A2Y4-2
	FRMD3	NM_001244960.2		c.121-65A>G		intron	N/A	NP_001231889.1	A2A2Y4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.253-65A>G		intron	N/A	ENSP00000303508.3	A2A2Y4-1
	FRMD3	ENST00000621208.4	TSL:1	c.121-65A>G		intron	N/A	ENSP00000484839.1	A2A2Y4-5
	FRMD3	ENST00000874519.1		c.253-65A>G		intron	N/A	ENSP00000544578.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66342 AN: 151010 Hom.: 15183 Cov.: 31

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

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

GnomAD4 genome AF: 0.440 AC: 66434 AN: 151102 Hom.: 15220 Cov.: 31 AF XY: 0.441 AC XY: 32528 AN XY: 73768

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

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
DANN	Benign	0.32
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3739657; hg19: chr9-85987935; COSMIC: COSV58457321;