chr21-46161921-C-G

Variant names:

• chr21-46161921-C-G
• NM_001142854.2:c.691G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142854.2(SPATC1L):​c.691G>C​(p.Glu231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPATC1L NM_001142854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

SPATC1L (HGNC:1298): (spermatogenesis and centriole associated 1 like) Enables identical protein binding activity. Predicted to act upstream of or within several processes, including actin polymerization or depolymerization; positive regulation of cAMP-dependent protein kinase activity; and positive regulation of protein kinase A signaling. Predicted to be located in sperm connecting piece. Predicted to be active in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069009244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATC1L	NM_001142854.2	c.691G>C	p.Glu231Gln	missense_variant	Exon 4 of 5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5	c.229G>C	p.Glu77Gln	missense_variant	Exon 3 of 4		NP_115637.3
SPATC1L	XM_005261188.6	c.691G>C	p.Glu231Gln	missense_variant	Exon 4 of 5		XP_005261245.1
SPATC1L	XM_011529756.3	c.349G>C	p.Glu117Gln	missense_variant	Exon 2 of 3		XP_011528058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6	c.691G>C	p.Glu231Gln	missense_variant	Exon 4 of 5	2	NM_001142854.2	ENSP00000291672.5
SPATC1L	ENST00000330205.10	c.229G>C	p.Glu77Gln	missense_variant	Exon 3 of 4	1		ENSP00000333869.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453902 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 723598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0034	.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.070	N;N
REVEL	Benign	0.023
Sift	Benign	0.43	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0	.;B
Vest4		0.16
MutPred		0.21		.;Loss of ubiquitination at K229 (P = 0.0609);
MVP		0.12
MPC		0.17
ClinPred		0.56	D
GERP RS		3.3
Varity_R		0.044
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47581835;