6-10893921-G-A

Variant names:

• chr6-10893921-G-A
• NM_001040274.3:c.133G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040274.3(SYCP2L):​c.133G>A​(p.Glu45Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYCP2L NM_001040274.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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]

ENSG00000272162 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35255253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2L	NM_001040274.3	c.133G>A	p.Glu45Lys	missense_variant	Exon 3 of 30	ENST00000283141.11	NP_001035364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP2L	ENST00000283141.11	c.133G>A	p.Glu45Lys	missense_variant	Exon 3 of 30	1	NM_001040274.3	ENSP00000283141.6
ENSG00000272162	ENST00000480294.1	n.*95G>A		non_coding_transcript_exon_variant	Exon 5 of 19	2		ENSP00000417929.1
ENSG00000272162	ENST00000480294.1	n.*95G>A		3_prime_UTR_variant	Exon 5 of 19	2		ENSP00000417929.1
SYCP2L	ENST00000341041.8	n.133G>A		non_coding_transcript_exon_variant	Exon 3 of 30	2		ENSP00000340320.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.133G>A (p.E45K) alteration is located in exon 3 (coding exon 3) of the SYCP2L gene. This alteration results from a G to A substitution at nucleotide position 133, causing the glutamic acid (E) at amino acid position 45 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	0.17
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0038	T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.22
Sift	Uncertain	0.024	D;.
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;.
Vest4		0.41
MutPred		0.31		Gain of MoRF binding (P = 0.0161);.;
MVP		0.42
MPC		0.57
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.19
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-10894154;