Variant chr1-114885560-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003176.4(SYCP1):c.936A>C(p.Gln312His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SYCP1
NM_003176.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Variant links:

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 links:

SYCP1 (HGNC:):

SYCP1 links:

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ACMG classification

Classification made for transcript

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=0.08675411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP1	NM_003176.4 linkuse as main transcript	c.936A>C	p.Gln312His	missense_variant	13/32	ENST00000369522.8	NP_003167.2	Q15431A0A024R0I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8 linkuse as main transcript	c.936A>C	p.Gln312His	missense_variant	13/32	1	NM_003176.4	ENSP00000358535.3		Q15431

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000431

AC:

AN:

231786

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000927

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.936A>C (p.Q312H) alteration is located in exon 13 (coding exon 12) of the SYCP1 gene. This alteration results from a A to C substitution at nucleotide position 936, causing the glutamine (Q) at amino acid position 312 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.078

T;.;T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.70

.;T;T;T;.

M_CAP

Benign

0.0068

MetaRNN

Benign

0.087

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N;.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N;.;.;N

REVEL

Benign

0.027

Sift

Uncertain

0.012

D;D;.;.;D

Sift4G

Uncertain

0.034

D;D;D;D;D

Polyphen

0.019

B;.;B;.;B

Vest4

0.19

MutPred

0.33

Loss of methylation at K316 (P = 0.0682);Loss of methylation at K316 (P = 0.0682);Loss of methylation at K316 (P = 0.0682);Loss of methylation at K316 (P = 0.0682);Loss of methylation at K316 (P = 0.0682);

MVP

0.082

MPC

0.35

ClinPred

0.42

GERP RS

2.6

Varity_R

0.11

gMVP

0.022

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over