10-48171029-C-A

Variant names:

• chr10-48171029-C-A
• NM_001018071.4:c.3403G>T

Variant summary

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

The NM_001018071.4(FRMPD2):​c.3403G>T​(p.Val1135Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1135M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.09

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.3403G>T	p.Val1135Leu	missense_variant	Exon 26 of 29	ENST00000374201.8	NP_001018081.4
FRMPD2	NM_001318191.1	c.3328G>T	p.Val1110Leu	missense_variant	Exon 24 of 27		NP_001305120.1
FRMPD2	NM_001042512.3	c.436G>T	p.Val146Leu	missense_variant	Exon 3 of 6		NP_001035977.3
FRMPD2	XM_017015744.2	c.259G>T	p.Val87Leu	missense_variant	Exon 3 of 6		XP_016871233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8	c.3403G>T	p.Val1135Leu	missense_variant	Exon 26 of 29	1	NM_001018071.4	ENSP00000363317.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 9

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3403G>T (p.V1135L) alteration is located in exon 26 (coding exon 26) of the FRMPD2 gene. This alteration results from a G to T substitution at nucleotide position 3403, causing the valine (V) at amino acid position 1135 to be replaced by a leucine (L). 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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	.;M;.
PhyloP100		5.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.7	.;D;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.60, 0.61
MutPred		0.68		Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);.;
MVP		0.37
MPC		3.1
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.54
gMVP		0.32
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

hg19: chr10-49379072;