9-83248238-C-T

Variant names:

• chr9-83248238-C-T
• rs765203567
• NM_174938.6:c.1474G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174938.6(FRMD3):​c.1474G>A​(p.Ala492Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: FRMD3 NM_174938.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34
• Publications: 3 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]

FRMD3-AS1 (HGNC:55790): (FRMD3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14727324).

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.1474G>A	p.Ala492Thr	missense	Exon 14 of 14	NP_777598.3
	FRMD3	NM_001244959.2		c.1474G>A	p.Ala492Thr	missense	Exon 14 of 15	NP_001231888.1	A2A2Y4-2
	FRMD3	NM_001244960.2		c.1342G>A	p.Ala448Thr	missense	Exon 14 of 14	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.1474G>A	p.Ala492Thr	missense	Exon 14 of 14	ENSP00000303508.3	A2A2Y4-1
	FRMD3	ENST00000621208.4	TSL:1	c.1342G>A	p.Ala448Thr	missense	Exon 14 of 14	ENSP00000484839.1	A2A2Y4-5
	FRMD3	ENST00000376434.5	TSL:1	c.892G>A	p.Ala298Thr	missense	Exon 9 of 10	ENSP00000365617.1	A2A2Y4-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249532 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1461890 Hom.: 0 Cov.: 34 AF XY: 0.0000550 AC XY: 40 AN XY: 727246

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1112012

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.074
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.40
Sift	Benign	0.28	T
Sift4G	Benign	0.14	T
Polyphen		0.60	P
Vest4		0.24
MutPred		0.39		Loss of helix (P = 0.0558)
MVP		0.76
MPC		0.70
ClinPred		0.24	T
GERP RS		5.7
Varity_R		0.15
gMVP		0.50
Mutation Taster		=73/27	polymorphism

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: rs765203567; hg19: chr9-85863153; COSMIC: COSV104409716;