chr9-83436354-A-C

Variant names:

• chr9-83436354-A-C
• rs10868008
• NM_174938.6:c.148-46646T>G

Variant summary

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

The NM_174938.6(FRMD3):​c.148-46646T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 152,184 control chromosomes in the GnomAD database, including 612 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 0.084 (612 hom., cov: 31)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	NM_174938.6	MANE Select	c.148-46646T>G		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.148-46646T>G		intron	N/A	NP_001231888.1
	FRMD3	NM_001244960.2		c.15+31264T>G		intron	N/A	NP_001231889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.148-46646T>G		intron	N/A	ENSP00000303508.3
	FRMD3	ENST00000621208.4	TSL:1	c.15+31264T>G		intron	N/A	ENSP00000484839.1
	FRMD3	ENST00000376438.5	TSL:2	c.148-46646T>G		intron	N/A	ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 12767 AN: 152066 Hom.: 615 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0707

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0759

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

GnomAD4 genome AF: 0.0839 AC: 12766 AN: 152184 Hom.: 612 Cov.: 31 AF XY: 0.0857 AC XY: 6373 AN XY: 74388

African (AFR) AF: 0.109 AC: 4538 AN: 41500

American (AMR) AF: 0.0619 AC: 946 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0707 AC: 245 AN: 3464

East Asian (EAS) AF: 0.0941 AC: 487 AN: 5176

South Asian (SAS) AF: 0.200 AC: 967 AN: 4824

European-Finnish (FIN) AF: 0.0589 AC: 624 AN: 10594

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0687 AC: 4675 AN: 68012

Other (OTH) AF: 0.0751 AC: 159 AN: 2116

Alfa AF: 0.0786 Hom.: 302

Bravo AF: 0.0816

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.60
PhyloP100		1.2
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: rs10868008; hg19: chr9-86051269;