dbSNP rs61732416: SPATA31F1:p.Arg1300Trp (chr9-34723342-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001141917.2(SPATA31F1):c.3898C>T(p.Arg1300Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,551,694 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 33 hom. )

Consequence

SPATA31F1
NM_001141917.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

SPATA31F1 (HGNC:41911): (SPATA31 subfamily F member 1) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31F1 links:

PHF24 (HGNC:29180): (PHD finger protein 24) Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including detection of mechanical stimulus involved in sensory perception of pain; gamma-aminobutyric acid signaling pathway; and regulation of GABAergic synaptic transmission. [provided by Alliance of Genome Resources, Apr 2022]

PHF24 links:

ENSG00000288583 (HGNC:):

ENSG00000288583 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053033233).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SPATA31F1	NM_001141917.2 link	c.3898C>T	p.Arg1300Trp	missense_variant	Exon 4 of 4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1 link	c.133+20304G>A		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1 link	c.70+20304G>A		intron_variant	Intron 2 of 9		XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM205A	ENST00000378788.4 link	c.3898C>T	p.Arg1300Trp	missense_variant	Exon 4 of 4	2	NM_001141917.2	ENSP00000417711.1		Q6ZU69
ENSG00000288583	ENST00000664167.1 link	n.86+20304G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

541

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00606

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00360

AC:

563

AN:

156344

Hom.:

AF XY:

0.00351

AC XY:

291

AN XY:

82870

show subpopulations

Gnomad AFR exome

AF:

0.00189

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.00678

Gnomad OTH exome

AF:

0.00251

GnomAD4 exome

AF:

0.00633

AC:

8855

AN:

1399406

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

4265

AN XY:

690208

show subpopulations

Gnomad4 AFR exome

AF:

0.000981

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00198

Gnomad4 FIN exome

AF:

0.00434

Gnomad4 NFE exome

AF:

0.00749

Gnomad4 OTH exome

AF:

0.00531

GnomAD4 genome

AF:

0.00355

AC:

540

AN:

152288

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00606

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00582

Hom.:

Bravo

AF:

0.00342

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00691

AC:

ExAC

AF:

0.00296

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.8

DANN

Benign

0.79

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.55

M_CAP

Benign

0.014

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.035

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.84

REVEL

Benign

0.081

Sift

Benign

0.14

Sift4G

Benign

0.085

Polyphen

0.0030

Vest4

0.075

MVP

0.17

ClinPred

0.0014

GERP RS

-0.85

Varity_R

0.035

gMVP

0.073

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over