9-83473380-C-T

Variant names:

• chr9-83473380-C-T
• rs12551710
• NM_174938.6:c.147+64705G>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+64705G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 152,314 control chromosomes in the GnomAD database, including 323 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 0.060 (323 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 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+64705G>A		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.147+64705G>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+64705G>A		intron	N/A	ENSP00000303508.3	A2A2Y4-1
	FRMD3	ENST00000874519.1		c.147+64705G>A		intron	N/A	ENSP00000544578.1
	FRMD3	ENST00000962006.1		c.147+64705G>A		intron	N/A	ENSP00000632065.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9053 AN: 152196 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0595 AC: 9063 AN: 152314 Hom.: 323 Cov.: 32 AF XY: 0.0607 AC XY: 4519 AN XY: 74472

African (AFR) AF: 0.0377 AC: 1568 AN: 41560

American (AMR) AF: 0.0478 AC: 732 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3468

East Asian (EAS) AF: 0.181 AC: 935 AN: 5178

South Asian (SAS) AF: 0.0829 AC: 400 AN: 4824

European-Finnish (FIN) AF: 0.0578 AC: 614 AN: 10622

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4468 AN: 68038

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0580 Hom.: 131

Bravo AF: 0.0570

Asia WGS AF: 0.121 AC: 418 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	2.5
DANN	Benign	0.71
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: rs12551710; hg19: chr9-86088295;