9-83299328-A-C

Position:

• chr9-83299328-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174938.6(FRMD3):​c.927-142T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 582,874 control chromosomes in the GnomAD database, including 99,029 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 0.49 (20519 hom., cov: 33)
  • Exomes 𝑓: 0.60 (78510 hom.)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD3	NM_174938.6	c.927-142T>G		intron_variant		ENST00000304195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD3	ENST00000304195.8	c.927-142T>G		intron_variant		1	NM_174938.6	P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74002 AN: 152006 Hom.: 20510 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.598 AC: 257552 AN: 430750 Hom.: 78510 AF XY: 0.602 AC XY: 136235 AN XY: 226416

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.487 AC: 74031 AN: 152124 Hom.: 20519 Cov.: 33 AF XY: 0.491 AC XY: 36523 AN XY: 74348

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.541

Alfa AF: 0.586 Hom.: 52755

Bravo AF: 0.466

Asia WGS AF: 0.623 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.43

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: rs1359168; hg19: chr9-85914243;