Genetic Variant SPATA31F1:p.Met499Leu (chr9-34725745-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001141917.2(SPATA31F1):c.1495A>T(p.Met499Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M499I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31F1
NM_001141917.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.497

Publications

23 publications found

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:

ENSG00000230074 (HGNC:):

ENSG00000230074 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037671626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SPATA31F1	NM_001141917.2 link	c.1495A>T	p.Met499Leu	missense_variant	Exon 4 of 4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1 link	c.133+22707T>A		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1 link	c.70+22707T>A		intron_variant	Intron 2 of 9		XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31F1	ENST00000378788.4 link	c.1495A>T	p.Met499Leu	missense_variant	Exon 4 of 4	2	NM_001141917.2	ENSP00000417711.1		Q6ZU69

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1396878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688364

African (AFR)

AF:

0.00

AC:

AN:

31584

American (AMR)

AF:

0.00

AC:

AN:

35670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25132

East Asian (EAS)

AF:

0.00

AC:

AN:

35660

South Asian (SAS)

AF:

0.00

AC:

AN:

79152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076892

Other (OTH)

AF:

0.00

AC:

AN:

57884

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.87

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.075

M_CAP

Benign

0.0049

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

PhyloP100

-0.50

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.18

REVEL

Benign

0.018

Sift

Benign

0.12

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.10

MutPred

0.12

Loss of helix (P = 0.1299);

MVP

0.014

ClinPred

0.030

GERP RS

-1.3

Varity_R

0.10

gMVP

0.080

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over