NM_001018071.4:c.3403G>T

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

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Other links and lift over

hg19: chr10-49379072;