Genetic Variant SPOCD1:p.Arg1181His (chr1-31790712-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_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. 16/22 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

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.678

Publications

2 publications found

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]

SPOCD1 links:

ENSG00000254545 (HGNC:):

ENSG00000254545 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

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 VariationId is 2354459.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144569.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPOCD1	NM_144569.7	MANE Select	c.3542G>A	p.Arg1181His	missense	Exon 16 of 16	NP_653170.3
SPOCD1	NM_001281987.3		c.3503G>A	p.Arg1168His	missense	Exon 16 of 16	NP_001268916.1	Q6ZMY3-2
SPOCD1	NM_001281988.3		c.1982G>A	p.Arg661His	missense	Exon 15 of 15	NP_001268917.1	Q6ZMY3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPOCD1	ENST00000360482.7	TSL:2 MANE Select	c.3542G>A	p.Arg1181His	missense	Exon 16 of 16	ENSP00000353670.2	Q6ZMY3-1
SPOCD1	ENST00000533231.5	TSL:5	c.3503G>A	p.Arg1168His	missense	Exon 15 of 15	ENSP00000435851.1	Q6ZMY3-2
SPOCD1	ENST00000917879.1		c.3500G>A	p.Arg1167His	missense	Exon 15 of 15	ENSP00000587938.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152184

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000198

AC:

AN:

156288

AF XY:

0.000206

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 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.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

690344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31618

American (AMR)

AF:

0.0000840

AC:

AN:

35718

Ashkenazi Jewish (ASJ)

AF:

0.00163

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35760

South Asian (SAS)

AF:

0.0000757

AC:

AN:

79252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49268

Middle Eastern (MID)

AF:

0.00246

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

1079076

Other (OTH)

AF:

0.000259

AC:

AN:

58018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.000458

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000322

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000736

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.39

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.00085

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.44

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

-0.68

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

REVEL

Benign

0.0030

Sift

Benign

0.57

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.030

MutPred

0.12

Loss of helix (P = 0.0376)

MVP

0.22

MPC

0.18

ClinPred

0.0026

GERP RS

-1.3

Varity_R

0.016

gMVP

0.060

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over