21-46161594-C-A

Position:

• chr21-46161594-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142854.2(SPATC1L):​c.808G>T​(p.Val270Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,610,254 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (157 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (157 hom.)
• Consequence: SPATC1L NM_001142854.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.464

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021375418).
• BP6: Variant 21-46161594-C-A is Benign according to our data. Variant chr21-46161594-C-A is described in ClinVar as [Benign]. Clinvar id is 769141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATC1L	NM_001142854.2	c.808G>T	p.Val270Leu	missense_variant	5/5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5	c.346G>T	p.Val116Leu	missense_variant	4/4		NP_115637.3
SPATC1L	XM_005261188.6	c.808G>T	p.Val270Leu	missense_variant	5/5		XP_005261245.1
SPATC1L	XM_011529756.3	c.466G>T	p.Val156Leu	missense_variant	3/3		XP_011528058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6	c.808G>T	p.Val270Leu	missense_variant	5/5	2	NM_001142854.2	ENSP00000291672	P1
SPATC1L	ENST00000330205.10	c.346G>T	p.Val116Leu	missense_variant	4/4	1		ENSP00000333869

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3726 AN: 152086 Hom.: 155 Cov.: 31

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00628 AC: 1503 AN: 239406 Hom.: 65 AF XY: 0.00466 AC XY: 610 AN XY: 130866

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.00450

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000215

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.00256 AC: 3734 AN: 1458050 Hom.: 157 Cov.: 33 AF XY: 0.00221 AC XY: 1605 AN XY: 725180

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.00527

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.0246 AC: 3743 AN: 152204 Hom.: 157 Cov.: 31 AF XY: 0.0238 AC XY: 1775 AN XY: 74430

Gnomad4 AFR AF: 0.0845

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00129 Hom.: 3

Bravo AF: 0.0287

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0924 AC: 406

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.00788 AC: 949

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 29, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	-0.077
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.51	D
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	.;N
MutationTaster	Benign	0.94	N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.038
Sift	Benign	0.19	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.39	.;B
Vest4		0.12
MutPred		0.48		.;Gain of catalytic residue at V270 (P = 0.0179);
MVP		0.27
MPC		0.20
ClinPred		0.011	T
GERP RS		4.3
Varity_R		0.15
gMVP		0.59

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

LitVar

Other links and lift over

dbSNP: rs74518516; hg19: chr21-47581508;