rs4877253

Positions:

• chr9-83349535-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD3	NM_174938.6	c.374+144T>C		intron_variant		ENST00000304195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD3	ENST00000304195.8	c.374+144T>C		intron_variant		1	NM_174938.6	P1
FRMD3	ENST00000621208.4	c.242+144T>C		intron_variant		1
FRMD3	ENST00000376438.5	c.374+144T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47410 AN: 151984 Hom.: 7767 Cov.: 32

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

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.312 AC: 47431 AN: 152102 Hom.: 7771 Cov.: 32 AF XY: 0.310 AC XY: 23054 AN XY: 74374

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.0808

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.291

Alfa AF: 0.335 Hom.: 2486

Bravo AF: 0.305

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.64

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: rs4877253; hg19: chr9-85964450;