1-31790712-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144569.7(SPOCD1):​c.3542G>A​(p.Arg1181His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,551,774 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

SPOCD1
NM_144569.7 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.678
Variant links:
Genes affected
SPOCD1 (HGNC:26338): (SPOC domain containing 1) This gene encodes a protein that belongs to the TFIIS family of transcription factors. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.00988999).
BP6
Variant 1-31790712-C-T is Benign according to our data. Variant chr1-31790712-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2354459.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPOCD1NM_144569.7 linkc.3542G>A p.Arg1181His missense_variant Exon 16 of 16 ENST00000360482.7 NP_653170.3 Q6ZMY3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPOCD1ENST00000360482.7 linkc.3542G>A p.Arg1181His missense_variant Exon 16 of 16 2 NM_144569.7 ENSP00000353670.2 Q6ZMY3-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000198
AC:
31
AN:
156288
Hom.:
1
AF XY:
0.000206
AC XY:
17
AN XY:
82386
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000404
Gnomad ASJ exome
AF:
0.00164
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000198
Gnomad OTH exome
AF:
0.000226
GnomAD4 exome
AF:
0.000104
AC:
145
AN:
1399590
Hom.:
1
Cov.:
31
AF XY:
0.000110
AC XY:
76
AN XY:
690344
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000840
Gnomad4 ASJ exome
AF:
0.00163
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000757
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.000259
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000322
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.0000736
AC:
7

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 07, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.39
DANN
Benign
0.56
DEOGEN2
Benign
0.00085
.;T;T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0078
N
LIST_S2
Benign
0.44
T;T;T;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.0099
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
.;N;.;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.0
N;N;N;N
REVEL
Benign
0.0030
Sift
Benign
0.57
T;T;T;T
Sift4G
Benign
0.37
T;T;T;T
Polyphen
0.0
.;B;B;B
Vest4
0.030
MutPred
0.12
.;Loss of helix (P = 0.0376);.;.;
MVP
0.22
MPC
0.18
ClinPred
0.0026
T
GERP RS
-1.3
Varity_R
0.016
gMVP
0.060

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: rs754159686; hg19: chr1-32256313; COSMIC: COSV57096251; COSMIC: COSV57096251; API