rs1330512159

Variant names:

• chr10-48163430-C-T
• rs1330512159
• NM_001018071.4:c.3779G>A

Variant summary

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

The NM_001018071.4(FRMPD2):​c.3779G>A​(p.Cys1260Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000062 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 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=0.07063162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.3779G>A	p.Cys1260Tyr	missense_variant	Exon 28 of 29	ENST00000374201.8	NP_001018081.4
FRMPD2	NM_001318191.1	c.3704G>A	p.Cys1235Tyr	missense_variant	Exon 26 of 27		NP_001305120.1
FRMPD2	NM_001042512.3	c.812G>A	p.Cys271Tyr	missense_variant	Exon 5 of 6		NP_001035977.3
FRMPD2	XM_017015744.2	c.635G>A	p.Cys212Tyr	missense_variant	Exon 5 of 6		XP_016871233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8	c.3779G>A	p.Cys1260Tyr	missense_variant	Exon 28 of 29	1	NM_001018071.4	ENSP00000363317.3

Frequencies

GnomAD3 genomes AF: 0.0000275 AC: 4 AN: 145500 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000450

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000582 AC: 3 AN: 51546 AF XY: 0.0000387

Gnomad AFR exome AF: 0.00

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: 0.000152

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000619 AC: 54 AN: 872974 Hom.: 0 Cov.: 12 AF XY: 0.0000590 AC XY: 27 AN XY: 457650

African (AFR) AF: 0.00 AC: 0 AN: 21394

American (AMR) AF: 0.00 AC: 0 AN: 43956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22274

East Asian (EAS) AF: 0.00 AC: 0 AN: 36812

South Asian (SAS) AF: 0.00 AC: 0 AN: 73876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2994

European-Non Finnish (NFE) AF: 0.0000883 AC: 51 AN: 577766

Other (OTH) AF: 0.0000736 AC: 3 AN: 40740

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000275 AC: 4 AN: 145500 Hom.: 0 Cov.: 27 AF XY: 0.0000141 AC XY: 1 AN XY: 70780

African (AFR) AF: 0.0000263 AC: 1 AN: 38094

American (AMR) AF: 0.00 AC: 0 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000450 AC: 3 AN: 66632

Other (OTH) AF: 0.00 AC: 0 AN: 1970

Alfa AF: 0.0000712 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3779G>A (p.C1260Y) alteration is located in exon 28 (coding exon 28) of the FRMPD2 gene. This alteration results from a G to A substitution at nucleotide position 3779, causing the cysteine (C) at amino acid position 1260 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.32
DEOGEN2	Benign	0.030	T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	.;N;.
PhyloP100		1.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	.;D;D
REVEL	Benign	0.024
Sift	Benign	0.39	.;T;T
Sift4G	Benign	0.46	.;T;T
Polyphen		0.0060, 0.0040	.;B;B
Vest4		0.22, 0.18
MVP		0.25
MPC		2.5
ClinPred		0.037	T
GERP RS		1.9
Varity_R		0.081
gMVP		0.17
Mutation Taster		=96/4	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: rs1330512159; hg19: chr10-49371473;