21-46161702-A-G

Position:

• chr21-46161702-A-G

Variant summary

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

The NM_001142854.2(SPATC1L):​c.700T>C​(p.Ser234Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATC1L NM_001142854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATC1L	NM_001142854.2	c.700T>C	p.Ser234Pro	missense_variant	5/5	ENST00000291672.6
SPATC1L	NM_032261.5	c.238T>C	p.Ser80Pro	missense_variant	4/4
SPATC1L	XM_005261188.6	c.700T>C	p.Ser234Pro	missense_variant	5/5
SPATC1L	XM_011529756.3	c.358T>C	p.Ser120Pro	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATC1L	ENST00000291672.6	c.700T>C	p.Ser234Pro	missense_variant	5/5	2	NM_001142854.2	P1
SPATC1L	ENST00000330205.10	c.238T>C	p.Ser80Pro	missense_variant	4/4	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434416 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 710306

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.700T>C (p.S234P) alteration is located in exon 5 (coding exon 4) of the SPATC1L gene. This alteration results from a T to C substitution at nucleotide position 700, causing the serine (S) at amino acid position 234 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.082
FATHMM_MKL	Benign	0.57	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.92	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.071	T;T
Polyphen		0.0040	.;B
Vest4		0.63
MVP		0.32
MPC		0.23
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47581616;