1-114858674-T-C

Position:

• chr1-114858674-T-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.419T>C​(p.Ile140Thr) 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. 14/21 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: 1.68

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=0.13331482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP1	NM_003176.4	c.419T>C	p.Ile140Thr	missense_variant	6/32	ENST00000369522.8	NP_003167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8	c.419T>C	p.Ile140Thr	missense_variant	6/32	1	NM_003176.4	ENSP00000358535.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 18, 2023

The c.419T>C (p.I140T) alteration is located in exon 6 (coding exon 5) of the SYCP1 gene. This alteration results from a T to C substitution at nucleotide position 419, causing the isoleucine (I) at amino acid position 140 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	0.19
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.062	T;.;T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.79	.;T;T;T;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M;.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.55	N;N;.;.;N
REVEL	Benign	0.15
Sift	Benign	0.55	T;T;.;.;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.37	B;.;B;.;B
Vest4		0.14
MutPred		0.41		Gain of phosphorylation at I140 (P = 0.021);Gain of phosphorylation at I140 (P = 0.021);Gain of phosphorylation at I140 (P = 0.021);Gain of phosphorylation at I140 (P = 0.021);Gain of phosphorylation at I140 (P = 0.021);
MVP		0.082
MPC		0.29
ClinPred		0.34	T
GERP RS		5.3
Varity_R		0.26
gMVP		0.089

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: chr1-115401295;