chr6-10907647-A-C

Variant names:

• chr6-10907647-A-C
• rs771312169
• NM_001040274.3:c.782A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040274.3(SYCP2L):​c.782A>C​(p.Glu261Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYCP2L NM_001040274.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22
• Publications: 0 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

ENSG00000272162 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16407421).

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.782A>C	p.Glu261Ala	missense	Exon 10 of 30	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.782A>C	p.Glu261Ala	missense	Exon 10 of 30	ENSP00000283141.6	Q5T4T6-1
	ENSG00000272162	ENST00000480294.1	TSL:2	n.*744A>C		non_coding_transcript_exon	Exon 12 of 19	ENSP00000417929.1	F8WBI7
	ENSG00000272162	ENST00000480294.1	TSL:2	n.*744A>C		3_prime_UTR	Exon 12 of 19	ENSP00000417929.1	F8WBI7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247732 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460364 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726494

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111622

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.2
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.087
Sift	Benign	0.27	T
Sift4G	Benign	0.063	T
Polyphen		0.79	P
Vest4		0.36
MutPred		0.24		Loss of disorder (P = 0.086)
MVP		0.63
MPC		0.42
ClinPred		0.67	D
GERP RS		2.8
Varity_R		0.14
gMVP		0.24
Mutation Taster		=90/10	polymorphism

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: rs771312169; hg19: chr6-10907880;