chr9-83504130-G-T

Variant names:

• chr9-83504130-G-T
• rs4877785
• NM_174938.6:c.147+33955C>A

Variant summary

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

The NM_174938.6(FRMD3):​c.147+33955C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,830 control chromosomes in the GnomAD database, including 13,871 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 0.41 (13871 hom., cov: 31)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 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.147+33955C>A		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.147+33955C>A		intron	N/A	NP_001231888.1	A2A2Y4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.147+33955C>A		intron	N/A	ENSP00000303508.3	A2A2Y4-1
	FRMD3	ENST00000874519.1		c.147+33955C>A		intron	N/A	ENSP00000544578.1
	FRMD3	ENST00000962006.1		c.147+33955C>A		intron	N/A	ENSP00000632065.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62532 AN: 151712 Hom.: 13866 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 62551 AN: 151830 Hom.: 13871 Cov.: 31 AF XY: 0.409 AC XY: 30350 AN XY: 74200

African (AFR) AF: 0.249 AC: 10304 AN: 41422

American (AMR) AF: 0.477 AC: 7284 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1463 AN: 5144

South Asian (SAS) AF: 0.450 AC: 2160 AN: 4804

European-Finnish (FIN) AF: 0.416 AC: 4394 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33712 AN: 67872

Other (OTH) AF: 0.448 AC: 943 AN: 2106

Alfa AF: 0.480 Hom.: 13213

Bravo AF: 0.410

Asia WGS AF: 0.426 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.72
DANN	Benign	0.74
PhyloP100		-0.17
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: rs4877785; hg19: chr9-86119045;