Genetic Variant SYCP1:p.Asn508Asn (chr1-114911577-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_003176.4(SYCP1):c.1524C>T(p.Asn508Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,483,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SYCP1
NM_003176.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.421

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 1-114911577-C-T is Benign according to our data. Variant chr1-114911577-C-T is described in ClinVar as Benign. ClinVar VariationId is 787212.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.421 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP1	NM_003176.4 link	c.1524C>T	p.Asn508Asn	synonymous_variant	Exon 18 of 32	ENST00000369522.8	NP_003167.2	Q15431A0A024R0I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8 link	c.1524C>T	p.Asn508Asn	synonymous_variant	Exon 18 of 32	1	NM_003176.4	ENSP00000358535.3		Q15431

Frequencies

GnomAD3 genomes

AF:

0.000928

AC:

141

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000555

AC:

107

AN:

192936

AF XY:

0.000501

show subpopulations

Gnomad AFR exome

AF:

0.00347

Gnomad AMR exome

AF:

0.000227

Gnomad ASJ exome

AF:

0.00510

Gnomad EAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000646

Gnomad OTH exome

AF:

0.000718

GnomAD4 exome

AF:

0.000268

AC:

357

AN:

1331784

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

185

AN XY:

658018

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

28518

American (AMR)

AF:

0.000249

AC:

AN:

32114

Ashkenazi Jewish (ASJ)

AF:

0.00438

AC:

102

AN:

23280

East Asian (EAS)

AF:

0.000183

AC:

AN:

32740

South Asian (SAS)

AF:

0.000237

AC:

AN:

59116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49050

Middle Eastern (MID)

AF:

0.000186

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.000126

AC:

132

AN:

1047002

Other (OTH)

AF:

0.000678

AC:

AN:

54600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000928

AC:

141

AN:

151988

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00274

AC:

114

AN:

41534

American (AMR)

AF:

0.000131

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00606

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67876

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000741

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 02, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.8

(source)

DANN

Benign

0.58

PhyloP100

0.42

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over