rs200627064

Variant names:

• chr6-33418157-C-G
• rs200627064
• ENST00000374500.10:c.-98G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-33418157-C-G
• chr6-33418157-C-T

Variant summary

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

The ENST00000374500.10(CUTA):​c.-98G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CUTA ENST00000374500.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 0 publications found

Genes affected

CUTA (HGNC:21101): (cutA divalent cation tolerance homolog) Enables enzyme binding activity. Involved in protein localization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYNGAP1 (HGNC:11497): (synaptic Ras GTPase activating protein 1) This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

SYNGAP1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• SYNGAP1-related developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

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=0.09152776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374500.10. 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
	CUTA	NM_001014840.2	MANE Select	c.-157G>C		upstream_gene	N/A	NP_001014840.1	O60888-1
	CUTA	NM_001014433.3		c.-98G>C		upstream_gene	N/A	NP_001014433.2	O60888-3
	CUTA	NM_001014837.2		c.-347G>C		upstream_gene	N/A	NP_001014837.1	O60888-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUTA	ENST00000374500.10	TSL:1	c.-98G>C		5_prime_UTR	Exon 1 of 6	ENSP00000363624.6	O60888-3
	CUTA	ENST00000492510.1	TSL:3	c.-81G>C		5_prime_UTR	Exon 1 of 2	ENSP00000499470.1
	CUTA	ENST00000879000.1		c.-87+45G>C		intron	N/A	ENSP00000549059.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.96
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.14
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.10
Sift	Benign	0.14	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.42	B
Vest4		0.23
MutPred		0.080		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.12
MPC		0.26
ClinPred		0.74	D
GERP RS		2.9
PromoterAI		0.0015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.43

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: rs200627064; hg19: chr6-33385934;