chr10-48171079-T-C

Variant names:

• chr10-48171079-T-C
• rs531740681
• NM_001018071.4:c.3353A>G

Variant summary

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

The NM_001018071.4(FRMPD2):​c.3353A>G​(p.Gln1118Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• 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=0.16823322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.3353A>G	p.Gln1118Arg	missense_variant	Exon 26 of 29	ENST00000374201.8	NP_001018081.4
FRMPD2	NM_001318191.1	c.3278A>G	p.Gln1093Arg	missense_variant	Exon 24 of 27		NP_001305120.1
FRMPD2	NM_001042512.3	c.386A>G	p.Gln129Arg	missense_variant	Exon 3 of 6		NP_001035977.3
FRMPD2	XM_017015744.2	c.209A>G	p.Gln70Arg	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.3353A>G	p.Gln1118Arg	missense_variant	Exon 26 of 29	1	NM_001018071.4	ENSP00000363317.3

Frequencies

GnomAD3 genomes AF: 0.000156 AC: 23 AN: 147196 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000343

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: 0.00103

GnomAD2 exomes AF: 0.000139 AC: 5 AN: 36052 AF XY: 0.000217

Gnomad AFR exome AF: 0.000858

Gnomad AMR exome AF: 0.000142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000284 AC: 20 AN: 704700 Hom.: 0 Cov.: 9 AF XY: 0.0000187 AC XY: 7 AN XY: 375108

African (AFR) AF: 0.000586 AC: 12 AN: 20464

American (AMR) AF: 0.000118 AC: 5 AN: 42330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20908

East Asian (EAS) AF: 0.00 AC: 0 AN: 35842

South Asian (SAS) AF: 0.00 AC: 0 AN: 70252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 425006

Other (OTH) AF: 0.0000853 AC: 3 AN: 35160

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000163 AC: 24 AN: 147314 Hom.: 0 Cov.: 23 AF XY: 0.000154 AC XY: 11 AN XY: 71430

African (AFR) AF: 0.000419 AC: 17 AN: 40620

American (AMR) AF: 0.000343 AC: 5 AN: 14580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66414

Other (OTH) AF: 0.00102 AC: 2 AN: 1962

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000212

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3353A>G (p.Q1118R) alteration is located in exon 26 (coding exon 26) of the FRMPD2 gene. This alteration results from a A to G substitution at nucleotide position 3353, causing the glutamine (Q) at amino acid position 1118 to be replaced by an arginine (R). 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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	.;M;.
PhyloP100		5.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	.;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	.;D;D
Sift4G	Uncertain	0.016	.;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.69, 0.59
MVP		0.45
MPC		3.2
ClinPred		0.23	T
GERP RS		3.3
Varity_R		0.29
gMVP		0.47
Mutation Taster		=85/15	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: rs531740681; hg19: chr10-49379122;