1-114878131-A-C

Position:

• chr1-114878131-A-C

Variant summary

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

The NM_003176.4(SYCP1):​c.839A>C​(p.Asn280Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYCP1 NM_003176.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

Genes affected

SYCP1 (HGNC:11487): (synaptonemal complex protein 1) Enables double-stranded DNA binding activity. Involved in protein homotetramerization. Predicted to be located in synaptonemal complex. Predicted to be active in central element; male germ cell nucleus; and transverse filament. [provided by Alliance of Genome Resources, Apr 2022]

SYCP1 (HGNC:):

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=0.20865643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP1	NM_003176.4	c.839A>C	p.Asn280Thr	missense_variant	12/32	ENST00000369522.8	NP_003167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8	c.839A>C	p.Asn280Thr	missense_variant	12/32	1	NM_003176.4	ENSP00000358535.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

Feb 10, 2022

The c.839A>C (p.N280T) alteration is located in exon 12 (coding exon 11) of the SYCP1 gene. This alteration results from a A to C substitution at nucleotide position 839, causing the asparagine (N) at amino acid position 280 to be replaced by a threonine (T). 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	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;T;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.64	.;T;T;T;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;M;.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N;N;.;.;N
REVEL	Benign	0.11
Sift	Benign	0.18	T;T;.;.;T
Sift4G	Benign	0.55	T;T;T;T;T
Polyphen		0.17	B;.;B;.;B
Vest4		0.15
MutPred		0.53		Gain of phosphorylation at N280 (P = 0.0392);Gain of phosphorylation at N280 (P = 0.0392);Gain of phosphorylation at N280 (P = 0.0392);Gain of phosphorylation at N280 (P = 0.0392);Gain of phosphorylation at N280 (P = 0.0392);
MVP		0.41
MPC		0.46
ClinPred		0.74	D
GERP RS		3.8
Varity_R		0.11
gMVP		0.036

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: chr1-115420752;