NM_015687.5:c.3007C>T

Variant names:

• chr6-75312825-G-A
• rs34807169
• NM_015687.5:c.3007C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015687.5(FILIP1):​c.3007C>T​(p.Pro1003Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00485 in 1,614,122 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (180 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (155 hom.)
• Consequence: FILIP1 NM_015687.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.24
• Publications: 6 publications found

Genes affected

FILIP1 (HGNC:21015): (filamin A interacting protein 1) This gene encodes a filamin A binding protein. The encoded protein promotes the degradation of filamin A and may regulate cortical neuron migration and dendritic spine morphology. Mice lacking a functional copy of this gene exhibit reduced dendritic spine length and altered excitatory signaling. [provided by RefSeq, Oct 2016]

TMEM30A-DT (HGNC:48985): (TMEM30A divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015980899).
• BP6: Variant 6-75312825-G-A is Benign according to our data. Variant chr6-75312825-G-A is described in ClinVar as Benign. ClinVar VariationId is 719710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015687.5. 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
	FILIP1	NM_015687.5	MANE Select	c.3007C>T	p.Pro1003Ser	missense	Exon 5 of 6	NP_056502.1	Q7Z7B0-1
	FILIP1	NM_001289987.3		c.3016C>T	p.Pro1006Ser	missense	Exon 6 of 7	NP_001276916.1
	FILIP1	NM_001300866.3		c.3007C>T	p.Pro1003Ser	missense	Exon 5 of 7	NP_001287795.1	Q7Z7B0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1	ENST00000237172.12	TSL:1 MANE Select	c.3007C>T	p.Pro1003Ser	missense	Exon 5 of 6	ENSP00000237172.7	Q7Z7B0-1
	FILIP1	ENST00000393004.6	TSL:1	c.3007C>T	p.Pro1003Ser	missense	Exon 5 of 7	ENSP00000376728.1	Q7Z7B0-2
	FILIP1	ENST00000370020.1	TSL:1	c.2710C>T	p.Pro904Ser	missense	Exon 3 of 4	ENSP00000359037.1	A0A075B6G6

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3840 AN: 152118 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00649 AC: 1632 AN: 251442 AF XY: 0.00448

Gnomad AFR exome AF: 0.0882

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00272 AC: 3979 AN: 1461886 Hom.: 155 Cov.: 35 AF XY: 0.00234 AC XY: 1704 AN XY: 727246

African (AFR) AF: 0.0938 AC: 3140 AN: 33478

American (AMR) AF: 0.00543 AC: 243 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86258

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

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.000118 AC: 131 AN: 1112006

Other (OTH) AF: 0.00666 AC: 402 AN: 60396

GnomAD4 genome AF: 0.0253 AC: 3845 AN: 152236 Hom.: 180 Cov.: 32 AF XY: 0.0240 AC XY: 1790 AN XY: 74436

African (AFR) AF: 0.0874 AC: 3629 AN: 41530

American (AMR) AF: 0.0104 AC: 159 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68024

Other (OTH) AF: 0.0189 AC: 40 AN: 2116

Alfa AF: 0.00988 Hom.: 114

Bravo AF: 0.0287

ESP6500AA AF: 0.0828 AC: 365

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00825 AC: 1001

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.0021
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.040
Sift	Benign	0.18	T
Sift4G	Benign	0.48	T
Polyphen		0.12	B
Vest4		0.10
MVP		0.68
MPC		0.22
ClinPred		0.014	T
GERP RS		5.1
Varity_R		0.054
gMVP		0.40
Mutation Taster		=97/3	polymorphism (auto)

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: rs34807169; hg19: chr6-76022541;