rs3739657

chr9-83373020-T-Cchr9-83373020-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD3	NM_174938.6	c.253-65A>G		intron_variant		ENST00000304195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD3	ENST00000304195.8	c.253-65A>G		intron_variant		1	NM_174938.6	P1
FRMD3	ENST00000621208.4	c.121-65A>G		intron_variant		1
FRMD3	ENST00000376438.5	c.253-65A>G		intron_variant		2

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

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.373

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.387

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

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.436

Alfa AF: 0.382 Hom.: 14930

Bravo AF: 0.443

Asia WGS AF: 0.375 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.3
Dann	Benign	0.32

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

LitVar

Other links and lift over

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