1-31790712-C-G

Variant names:

• chr1-31790712-C-G
• rs754159686
• NM_144569.7:c.3542G>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.3542G>C​(p.Arg1181Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,590 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. 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. R1181H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SPOCD1 NM_144569.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• 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=0.035456598).

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.3542G>C	p.Arg1181Pro	missense	Exon 16 of 16	NP_653170.3
	SPOCD1	NM_001281987.3		c.3503G>C	p.Arg1168Pro	missense	Exon 16 of 16	NP_001268916.1	Q6ZMY3-2
	SPOCD1	NM_001281988.3		c.1982G>C	p.Arg661Pro	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.3542G>C	p.Arg1181Pro	missense	Exon 16 of 16	ENSP00000353670.2	Q6ZMY3-1
	SPOCD1	ENST00000533231.5	TSL:5	c.3503G>C	p.Arg1168Pro	missense	Exon 15 of 15	ENSP00000435851.1	Q6ZMY3-2
	SPOCD1	ENST00000917879.1		c.3500G>C	p.Arg1167Pro	missense	Exon 15 of 15	ENSP00000587938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399590 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690344

African (AFR) AF: 0.00 AC: 0 AN: 31618

American (AMR) AF: 0.00 AC: 0 AN: 35718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35760

South Asian (SAS) AF: 0.00 AC: 0 AN: 79252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079076

Other (OTH) AF: 0.00 AC: 0 AN: 58018

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.20
DANN	Benign	0.44
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.68
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.036
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.14	B
Vest4		0.044
MutPred		0.14		Gain of loop (P = 0.0013)
MVP		0.15
MPC		0.23
ClinPred		0.060	T
GERP RS		-1.3
Varity_R		0.081
gMVP		0.084
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs754159686; hg19: chr1-32256313;