chr9-83471685-C-T

Variant names:

• chr9-83471685-C-T
• rs7850633
• NM_174938.6:c.147+66400G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_174938.6(FRMD3):​c.147+66400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,044 control chromosomes in the GnomAD database, including 18,510 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 0.49 (18510 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+66400G>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+66400G>A		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+66400G>A		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74265 AN: 151926 Hom.: 18490 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.489 AC: 74324 AN: 152044 Hom.: 18510 Cov.: 33 AF XY: 0.484 AC XY: 35943 AN XY: 74314

African (AFR) AF: 0.430 AC: 17824 AN: 41462

American (AMR) AF: 0.498 AC: 7615 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1405 AN: 5176

South Asian (SAS) AF: 0.467 AC: 2247 AN: 4812

European-Finnish (FIN) AF: 0.459 AC: 4848 AN: 10568

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36823 AN: 67958

Other (OTH) AF: 0.515 AC: 1087 AN: 2112

Alfa AF: 0.527 Hom.: 66447

Bravo AF: 0.491

Asia WGS AF: 0.427 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.4
DANN	Benign	0.79
PhyloP100		-0.18
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: rs7850633; hg19: chr9-86086600;