NM_174938.6:c.148-73505A>G

Variant names:

• chr9-83463213-T-C
• rs11140109
• NM_174938.6:c.148-73505A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174938.6(FRMD3):​c.148-73505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,212 control chromosomes in the GnomAD database, including 1,583 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 0.13 (1583 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.148-73505A>G		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.148-73505A>G		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000621208.4	c.15+4405A>G		intron_variant	Intron 1 of 13	1		ENSP00000484839.1
FRMD3	ENST00000376438.5	c.148-73505A>G		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20012 AN: 152094 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.132 AC: 20020 AN: 152212 Hom.: 1583 Cov.: 32 AF XY: 0.134 AC XY: 9971 AN XY: 74412

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.149

Alfa AF: 0.158 Hom.: 2438

Bravo AF: 0.125

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs11140109; hg19: chr9-86078128; COSMIC: COSV58457892;