NM_001018071.4:c.3026G>C

Variant names:

• chr10-48174919-C-G
• rs782232511
• NM_001018071.4:c.3026G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001018071.4(FRMPD2):​c.3026G>C​(p.Cys1009Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1009Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 1 publications found

Genes affected

FRMPD2 (HGNC:28572): (FERM and PDZ domain containing 2) This gene encodes a peripheral membrane protein and is located in a region of chromosome 10q that contains a segmental duplication. This copy of the gene is full-length and is in the telomeric duplicated region. Two other more centromerically proximal copies of the gene are partial and may represent pseudogenes. This full-length gene appears to function in the establishment and maintenance of cell polarization. The protein is recruited to cell-cell junctions in an E-cadherin-dependent manner, and is selectively localized at the basolateral membrane in polarized epithelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1264548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.3026G>C	p.Cys1009Ser	missense_variant	Exon 24 of 29	ENST00000374201.8	NP_001018081.4
FRMPD2	NM_001318191.1	c.2951G>C	p.Cys984Ser	missense_variant	Exon 22 of 27		NP_001305120.1
FRMPD2	NM_001042512.3	c.59G>C	p.Cys20Ser	missense_variant	Exon 1 of 6		NP_001035977.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8	c.3026G>C	p.Cys1009Ser	missense_variant	Exon 24 of 29	1	NM_001018071.4	ENSP00000363317.3

Frequencies

GnomAD3 genomes AF: 0.0000166 AC: 2 AN: 120260 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000178

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 553420 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 295994

African (AFR) AF: 0.00 AC: 0 AN: 17240

American (AMR) AF: 0.00 AC: 0 AN: 29882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18988

East Asian (EAS) AF: 0.00 AC: 0 AN: 32520

South Asian (SAS) AF: 0.00 AC: 0 AN: 58476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 315796

Other (OTH) AF: 0.00 AC: 0 AN: 29596

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000166 AC: 2 AN: 120260 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 56666

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31102

American (AMR) AF: 0.000178 AC: 2 AN: 11236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3076

East Asian (EAS) AF: 0.00 AC: 0 AN: 4226

South Asian (SAS) AF: 0.00 AC: 0 AN: 2962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58082

Other (OTH) AF: 0.00 AC: 0 AN: 1500

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.029	T;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.21	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.2	.;N;.
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.5	.;D;D
REVEL	Benign	0.10
Sift	Benign	0.13	.;T;T
Sift4G	Benign	0.73	.;T;T
Polyphen		0.98, 1.0	.;D;D
Vest4		0.18, 0.19
MutPred		0.43		Loss of stability (P = 0.0813);Loss of stability (P = 0.0813);.;
MVP		0.21
MPC		2.7
ClinPred		0.56	D
GERP RS		2.0
Varity_R		0.16
gMVP		0.13
Mutation Taster		=87/13	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: rs782232511; hg19: chr10-49382962;