chr9-83496327-C-T

Variant names:

• chr9-83496327-C-T
• rs12551103
• NM_174938.6:c.147+41758G>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+41758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,214 control chromosomes in the GnomAD database, including 295 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 0.051 (295 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+41758G>A		intron_variant	Intron 1 of 13	ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+41758G>A		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+41758G>A		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7723 AN: 152094 Hom.: 293 Cov.: 33

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0632

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0579

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

GnomAD4 genome AF: 0.0508 AC: 7726 AN: 152214 Hom.: 295 Cov.: 33 AF XY: 0.0518 AC XY: 3852 AN XY: 74416

African (AFR) AF: 0.0116 AC: 481 AN: 41548

American (AMR) AF: 0.0629 AC: 962 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5170

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4824

European-Finnish (FIN) AF: 0.0554 AC: 586 AN: 10586

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0596 AC: 4056 AN: 68006

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0588 Hom.: 1236

Bravo AF: 0.0502

Asia WGS AF: 0.121 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		0.038
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: rs12551103; hg19: chr9-86111242;