Genetic Variant NM_144569.7:c.3362A>G (chr1-31790892-T-C) – 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_144569.7(SPOCD1):c.3362A>G(p.Gln1121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,510 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SPOCD1
NM_144569.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.159

Publications

0 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:

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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=0.041024983).

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.3362A>G	p.Gln1121Arg	missense	Exon 16 of 16	NP_653170.3
SPOCD1	NM_001281987.3		c.3323A>G	p.Gln1108Arg	missense	Exon 16 of 16	NP_001268916.1	Q6ZMY3-2
SPOCD1	NM_001281988.3		c.1802A>G	p.Gln601Arg	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.3362A>G	p.Gln1121Arg	missense	Exon 16 of 16	ENSP00000353670.2	Q6ZMY3-1
SPOCD1	ENST00000533231.5	TSL:5	c.3323A>G	p.Gln1108Arg	missense	Exon 15 of 15	ENSP00000435851.1	Q6ZMY3-2
SPOCD1	ENST00000917879.1		c.3320A>G	p.Gln1107Arg	missense	Exon 15 of 15	ENSP00000587938.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709638

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32578

American (AMR)

AF:

0.00

AC:

AN:

40788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24024

East Asian (EAS)

AF:

0.00

AC:

AN:

39328

South Asian (SAS)

AF:

0.00

AC:

AN:

81256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097376

Other (OTH)

AF:

0.00

AC:

AN:

58930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.1

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.36

M_CAP

Benign

0.0077

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.16

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

REVEL

Benign

0.014

Sift

Benign

0.75

Sift4G

Benign

0.61

Polyphen

0.0010

Vest4

0.069

MutPred

0.16

Gain of MoRF binding (P = 0.05)

MVP

0.12

MPC

0.15

ClinPred

0.019

GERP RS

-0.70

Varity_R

0.037

gMVP

0.044

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over