9-83460496-C-T

Variant names:

• chr9-83460496-C-T
• rs4014024
• NM_174938.6:c.148-70788G>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.148-70788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,944 control chromosomes in the GnomAD database, including 21,551 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 0.53 (21551 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 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.148-70788G>A		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.148-70788G>A		intron	N/A	NP_001231888.1
	FRMD3	NM_001244960.2		c.15+7122G>A		intron	N/A	NP_001231889.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.148-70788G>A		intron	N/A	ENSP00000303508.3
	FRMD3	ENST00000621208.4	TSL:1	c.15+7122G>A		intron	N/A	ENSP00000484839.1
	FRMD3	ENST00000874519.1		c.148-70788G>A		intron	N/A	ENSP00000544578.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80341 AN: 151826 Hom.: 21536 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.529 AC: 80390 AN: 151944 Hom.: 21551 Cov.: 32 AF XY: 0.526 AC XY: 39108 AN XY: 74284

African (AFR) AF: 0.605 AC: 25089 AN: 41436

American (AMR) AF: 0.507 AC: 7728 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1168 AN: 5148

South Asian (SAS) AF: 0.425 AC: 2047 AN: 4814

European-Finnish (FIN) AF: 0.525 AC: 5538 AN: 10540

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35065 AN: 67962

Other (OTH) AF: 0.541 AC: 1142 AN: 2112

Alfa AF: 0.517 Hom.: 34995

Bravo AF: 0.530

Asia WGS AF: 0.351 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		0.13
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: rs4014024; hg19: chr9-86075411;