chr10-48163348-A-C

Variant names:

• chr10-48163348-A-C
• rs1163664502
• NM_001018071.4:c.3861T>G

Variant summary

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

The NM_001018071.4(FRMPD2):​c.3861T>G​(p.Cys1287Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.3861T>G	p.Cys1287Trp	missense_variant	Exon 28 of 29	ENST00000374201.8	NP_001018081.4
FRMPD2	NM_001318191.1	c.3786T>G	p.Cys1262Trp	missense_variant	Exon 26 of 27		NP_001305120.1
FRMPD2	NM_001042512.3	c.894T>G	p.Cys298Trp	missense_variant	Exon 5 of 6		NP_001035977.3
FRMPD2	XM_017015744.2	c.717T>G	p.Cys239Trp	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.3861T>G	p.Cys1287Trp	missense_variant	Exon 28 of 29	1	NM_001018071.4	ENSP00000363317.3

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148776 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

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: AS_VQSR AF: 0.0000205 AC: 19 AN: 927730 Hom.: 0 Cov.: 14 AF XY: 0.0000165 AC XY: 8 AN XY: 483492

African (AFR) AF: 0.00 AC: 0 AN: 22284

American (AMR) AF: 0.00 AC: 0 AN: 44046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22560

East Asian (EAS) AF: 0.000513 AC: 19 AN: 37056

South Asian (SAS) AF: 0.00 AC: 0 AN: 75114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3112

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 627906

Other (OTH) AF: 0.00 AC: 0 AN: 42462

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000672 AC: 1 AN: 148776 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 72496

African (AFR) AF: 0.00 AC: 0 AN: 39540

American (AMR) AF: 0.00 AC: 0 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67400

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3861T>G (p.C1287W) alteration is located in exon 28 (coding exon 28) of the FRMPD2 gene. This alteration results from a T to G substitution at nucleotide position 3861, causing the cysteine (C) at amino acid position 1287 to be replaced by a tryptophan (W). 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	0.30
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Benign	1.1	.;L;.
PhyloP100		2.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.7	.;D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		1.0	.;D;D
Vest4		0.56, 0.48
MutPred		0.49		Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);.;
MVP		0.77
MPC		3.6
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.73
gMVP		0.32
Mutation Taster		=83/17	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: rs1163664502; hg19: chr10-49371391;