chr1-114874508-G-A

Position:

• chr1-114874508-G-A

Variant summary

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

The NM_003176.4(SYCP1):​c.601G>A​(p.Glu201Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYCP1 NM_003176.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP1	NM_003176.4	c.601G>A	p.Glu201Lys	missense_variant, splice_region_variant	9/32	ENST00000369522.8	NP_003167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8	c.601G>A	p.Glu201Lys	missense_variant, splice_region_variant	9/32	1	NM_003176.4	ENSP00000358535.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1393916 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 695254

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.: 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

Mar 08, 2024

The c.601G>A (p.E201K) alteration is located in exon 9 (coding exon 8) of the SYCP1 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glutamic acid (E) at amino acid position 201 to be replaced by a lysine (K). 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	0.30
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T;.;T;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	.;D;D;D;.
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.5	M;.;M;.;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.8	N;N;.;.;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;.;.;D
Sift4G	Uncertain	0.031	D;D;D;T;D
Polyphen		1.0	D;.;D;.;D
Vest4		0.78
MutPred		0.67		Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);
MVP		0.28
MPC		0.30
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.88
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-115417129;