chr9-34723296-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001141917.2(SPATA31F1):​c.3944C>A​(p.Pro1315His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000047 in 1,551,694 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 1 hom. )

Consequence

SPATA31F1
NM_001141917.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.506
Variant links:
Genes affected
SPATA31F1 (HGNC:41911): (SPATA31 subfamily F member 1) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0139377415).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPATA31F1NM_001141917.2 linkuse as main transcriptc.3944C>A p.Pro1315His missense_variant 4/4 ENST00000378788.4
PHF24XM_047423102.1 linkuse as main transcriptc.133+20258G>T intron_variant
PHF24XM_047423103.1 linkuse as main transcriptc.70+20258G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPATA31F1ENST00000378788.4 linkuse as main transcriptc.3944C>A p.Pro1315His missense_variant 4/42 NM_001141917.2 P1
ENST00000664167.1 linkuse as main transcriptn.86+20258G>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000960
AC:
15
AN:
156246
Hom.:
0
AF XY:
0.000133
AC XY:
11
AN XY:
82832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000659
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000486
AC:
68
AN:
1399390
Hom.:
1
Cov.:
65
AF XY:
0.0000695
AC XY:
48
AN XY:
690206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000745
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.0000517
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152304
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.000477
AC:
12

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 03, 2021The c.3944C>A (p.P1315H) alteration is located in exon 4 (coding exon 4) of the FAM205A gene. This alteration results from a C to A substitution at nucleotide position 3944, causing the proline (P) at amino acid position 1315 to be replaced by a histidine (H). 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
Benign
0.13
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0078
T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.014
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.12
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.15
MutPred
0.11
Loss of loop (P = 0.0603);
MVP
0.21
ClinPred
0.66
D
GERP RS
-2.0
Varity_R
0.093
gMVP
0.11

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.

Other links and lift over

dbSNP: rs546555671; hg19: chr9-34723293; API