chr1-31790794-C-T

Variant names:

• chr1-31790794-C-T
• rs573897332
• NM_144569.7:c.3460G>A

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.3460G>A​(p.Glu1154Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000776 in 1,546,146 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: SPOCD1 NM_144569.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.444
• 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=0.018850386).

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.3460G>A	p.Glu1154Lys	missense	Exon 16 of 16	NP_653170.3
	SPOCD1	NM_001281987.3		c.3421G>A	p.Glu1141Lys	missense	Exon 16 of 16	NP_001268916.1	Q6ZMY3-2
	SPOCD1	NM_001281988.3		c.1900G>A	p.Glu634Lys	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.3460G>A	p.Glu1154Lys	missense	Exon 16 of 16	ENSP00000353670.2	Q6ZMY3-1
	SPOCD1	ENST00000533231.5	TSL:5	c.3421G>A	p.Glu1141Lys	missense	Exon 15 of 15	ENSP00000435851.1	Q6ZMY3-2
	SPOCD1	ENST00000917879.1		c.3418G>A	p.Glu1140Lys	missense	Exon 15 of 15	ENSP00000587938.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000661 AC: 1 AN: 151232 AF XY: 0.0000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000869

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000646 AC: 9 AN: 1393806 Hom.: 0 Cov.: 31 AF XY: 0.00000582 AC XY: 4 AN XY: 687318

African (AFR) AF: 0.00 AC: 0 AN: 31542

American (AMR) AF: 0.00 AC: 0 AN: 34992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24364

East Asian (EAS) AF: 0.00 AC: 0 AN: 35932

South Asian (SAS) AF: 0.00 AC: 0 AN: 78248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00000743 AC: 8 AN: 1076240

Other (OTH) AF: 0.0000173 AC: 1 AN: 57730

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000879 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.2
DANN	Benign	0.80
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.44
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.0090
Sift	Benign	0.70	T
Sift4G	Benign	0.42	T
Polyphen		0.27	B
Vest4		0.12
MutPred		0.25		Gain of MoRF binding (P = 0.0122)
MVP		0.21
MPC		0.17
ClinPred		0.069	T
GERP RS		-3.9
Varity_R		0.039
gMVP		0.12
Mutation Taster		=97/3	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: rs573897332; hg19: chr1-32256395; COSMIC: COSV57098039; COSMIC: COSV57098039;