6-10968908-G-T

Variant names:

• chr6-10968908-G-T
• rs4713103
• NM_001040274.3:c.*38-5044G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040274.3(SYCP2L):​c.*38-5044G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,016 control chromosomes in the GnomAD database, including 24,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24176 hom., cov: 32)
• Consequence: SYCP2L NM_001040274.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 22 publications found

Genes affected

SYCP2L (HGNC:21537): (synaptonemal complex protein 2 like) Predicted to be involved in meiotic nuclear division. Predicted to act upstream of or within negative regulation of cell death. Located in condensed chromosome, centromeric region and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SYCP2L Gene-Disease associations (from GenCC):

• premature ovarian failure 24

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040274.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP2L	NM_001040274.3	MANE Select	c.*38-5044G>T		intron	N/A	NP_001035364.2	Q5T4T6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP2L	ENST00000283141.11	TSL:1 MANE Select	c.*38-5044G>T		intron	N/A	ENSP00000283141.6	Q5T4T6-1
	SYCP2L	ENST00000341041.8	TSL:2	n.*1655-5044G>T		intron	N/A	ENSP00000340320.4	Q5T4T6-2
	SYCP2L	ENST00000465872.1	TSL:3	n.122-5044G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83867 AN: 151898 Hom.: 24123 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.537

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.552 AC: 83977 AN: 152016 Hom.: 24176 Cov.: 32 AF XY: 0.560 AC XY: 41610 AN XY: 74294

African (AFR) AF: 0.633 AC: 26246 AN: 41476

American (AMR) AF: 0.636 AC: 9717 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3470

East Asian (EAS) AF: 0.909 AC: 4699 AN: 5172

South Asian (SAS) AF: 0.708 AC: 3410 AN: 4814

European-Finnish (FIN) AF: 0.501 AC: 5291 AN: 10566

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30993 AN: 67934

Other (OTH) AF: 0.539 AC: 1135 AN: 2104

Alfa AF: 0.496 Hom.: 55128

Bravo AF: 0.565

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4713103; hg19: chr6-10969141;