1-31790892-T-G

Variant names:

• chr1-31790892-T-G
• rs1570140588
• NM_144569.7:c.3362A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144569.7(SPOCD1):​c.3362A>C​(p.Gln1121Pro) 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. Q1121R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPOCD1 NM_144569.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 0 publications found

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]

ENSG00000254545 (HGNC:):

ACMG classification

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=0.06508884).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCD1	NM_144569.7	MANE Select	c.3362A>C	p.Gln1121Pro	missense	Exon 16 of 16	NP_653170.3
	SPOCD1	NM_001281987.3		c.3323A>C	p.Gln1108Pro	missense	Exon 16 of 16	NP_001268916.1	Q6ZMY3-2
	SPOCD1	NM_001281988.3		c.1802A>C	p.Gln601Pro	missense	Exon 15 of 15	NP_001268917.1	Q6ZMY3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCD1	ENST00000360482.7	TSL:2 MANE Select	c.3362A>C	p.Gln1121Pro	missense	Exon 16 of 16	ENSP00000353670.2	Q6ZMY3-1
	SPOCD1	ENST00000533231.5	TSL:5	c.3323A>C	p.Gln1108Pro	missense	Exon 15 of 15	ENSP00000435851.1	Q6ZMY3-2
	SPOCD1	ENST00000917879.1		c.3320A>C	p.Gln1107Pro	missense	Exon 15 of 15	ENSP00000587938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.9
DANN	Benign	0.42
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.16
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.017
Sift	Benign	0.19	T
Sift4G	Benign	0.39	T
Polyphen		0.0030	B
Vest4		0.32
MutPred		0.12		Gain of glycosylation at Q1121 (P = 0.0382)
MVP		0.088
MPC		0.18
ClinPred		0.032	T
GERP RS		-0.70
Varity_R		0.094
gMVP		0.20
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1570140588; hg19: chr1-32256493;