chr9-83447515-G-A

Variant names:

• chr9-83447515-G-A
• rs6559725
• NM_174938.6:c.148-57807C>T

Variant summary

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

The NM_174938.6(FRMD3):​c.148-57807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,270 control chromosomes in the GnomAD database, including 756 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 0.090 (756 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 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.148-57807C>T		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.148-57807C>T		intron	N/A	NP_001231888.1	A2A2Y4-2
	FRMD3	NM_001244960.2		c.15+20103C>T		intron	N/A	NP_001231889.1	A2A2Y4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.148-57807C>T		intron	N/A	ENSP00000303508.3	A2A2Y4-1
	FRMD3	ENST00000621208.4	TSL:1	c.15+20103C>T		intron	N/A	ENSP00000484839.1	A2A2Y4-5
	FRMD3	ENST00000874519.1		c.148-57807C>T		intron	N/A	ENSP00000544578.1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13691 AN: 152152 Hom.: 759 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0900 AC: 13707 AN: 152270 Hom.: 756 Cov.: 33 AF XY: 0.0908 AC XY: 6764 AN XY: 74462

African (AFR) AF: 0.136 AC: 5659 AN: 41562

American (AMR) AF: 0.0639 AC: 978 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 226 AN: 3468

East Asian (EAS) AF: 0.0797 AC: 412 AN: 5170

South Asian (SAS) AF: 0.202 AC: 974 AN: 4820

European-Finnish (FIN) AF: 0.0501 AC: 532 AN: 10618

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0681 AC: 4632 AN: 68014

Other (OTH) AF: 0.0790 AC: 167 AN: 2114

Alfa AF: 0.0769 Hom.: 347

Bravo AF: 0.0890

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.54
PhyloP100		0.61
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: rs6559725; hg19: chr9-86062430;