chr1-114911577-C-G

Variant names:

• chr1-114911577-C-G
• rs148948913
• NM_003176.4:c.1524C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003176.4(SYCP1):​c.1524C>G​(p.Asn508Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N508N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SYCP1 NM_003176.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036618948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP1	NM_003176.4	c.1524C>G	p.Asn508Lys	missense_variant	Exon 18 of 32	ENST00000369522.8	NP_003167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8	c.1524C>G	p.Asn508Lys	missense_variant	Exon 18 of 32	1	NM_003176.4	ENSP00000358535.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331790 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 658022

African (AFR) AF: 0.00 AC: 0 AN: 28518

American (AMR) AF: 0.00 AC: 0 AN: 32114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23282

East Asian (EAS) AF: 0.00 AC: 0 AN: 32740

South Asian (SAS) AF: 0.00 AC: 0 AN: 59116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1047006

Other (OTH) AF: 0.00 AC: 0 AN: 54600

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.6
DANN	Benign	0.29
DEOGEN2	Benign	0.039	T;.;T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.67	.;T;T;T;.
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.037	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.090	N;.;N;.;N
PhyloP100		0.42
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.56	N;N;.;.;N
REVEL	Benign	0.011
Sift	Benign	0.72	T;T;.;.;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0020	B;.;B;.;B
Vest4		0.14
MutPred		0.38		Gain of ubiquitination at N508 (P = 0.0109);Gain of ubiquitination at N508 (P = 0.0109);Gain of ubiquitination at N508 (P = 0.0109);Gain of ubiquitination at N508 (P = 0.0109);Gain of ubiquitination at N508 (P = 0.0109);
MVP		0.043
MPC		0.21
ClinPred		0.038	T
GERP RS		-0.34
Varity_R		0.050
gMVP		0.037
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148948913; hg19: chr1-115454198;