chr9-37707505-C-G

Variant names:

• chr9-37707505-C-G
• rs141611918
• NM_014907.3:c.191C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014907.3(FRMPD1):​c.191C>G​(p.Thr64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: FRMPD1 NM_014907.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.235
• Publications: 2 publications found

Genes affected

FRMPD1 (HGNC:29159): (FERM and PDZ domain containing 1) Involved in establishment of protein localization to membrane and regulation of G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of protein-containing complex. Colocalizes with cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255872 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01946038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014907.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD1	NM_014907.3	MANE Select	c.191C>G	p.Thr64Ser	missense	Exon 3 of 16	NP_055722.2	Q5SYB0-1
	FRMPD1	NM_001371223.1		c.191C>G	p.Thr64Ser	missense	Exon 3 of 16	NP_001358152.1	Q5SYB0-1
	FRMPD1	NM_001371224.1		c.191C>G	p.Thr64Ser	missense	Exon 4 of 17	NP_001358153.1	Q5SYB0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD1	ENST00000377765.8	TSL:1 MANE Select	c.191C>G	p.Thr64Ser	missense	Exon 3 of 16	ENSP00000366995.3	Q5SYB0-1
	FRMPD1	ENST00000539465.5	TSL:1	c.191C>G	p.Thr64Ser	missense	Exon 3 of 16	ENSP00000444411.1	Q5SYB0-1
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*1012-14240G>C		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000187 AC: 47 AN: 251390 AF XY: 0.000169

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000382 AC: 559 AN: 1461612 Hom.: 0 Cov.: 31 AF XY: 0.000366 AC XY: 266 AN XY: 727120

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000490 AC: 545 AN: 1111756

Other (OTH) AF: 0.0000994 AC: 6 AN: 60386

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74494

African (AFR) AF: 0.000120 AC: 5 AN: 41582

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000536 Hom.: 0

Bravo AF: 0.000264

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000545

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.33	N
PhyloP100		-0.23
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.094
Sift	Benign	0.10	T
Sift4G	Benign	0.29	T
Polyphen		0.0020	B
Vest4		0.084
MutPred		0.36		Loss of loop (P = 0.0804)
MVP		0.30
MPC		0.13
ClinPred		0.013	T
GERP RS		0.28
Varity_R		0.051
gMVP		0.16
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: rs141611918; hg19: chr9-37707502;