chr11-18612342-T-C

Variant names:

• chr11-18612342-T-C
• NM_194285.3:c.1858A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_194285.3(SPTY2D1):​c.1858A>G​(p.Arg620Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPTY2D1 NM_194285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

Genes affected

SPTY2D1 (HGNC:26818): (SPT2 chromatin protein domain containing 1) Enables DNA binding activity and histone binding activity. Involved in nucleosome organization; regulation of chromatin assembly; and regulation of transcription, DNA-templated. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194285.3. 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
	SPTY2D1	NM_194285.3	MANE Select	c.1858A>G	p.Arg620Gly	missense	Exon 4 of 6	NP_919261.2	Q68D10-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTY2D1	ENST00000336349.6	TSL:1 MANE Select	c.1858A>G	p.Arg620Gly	missense	Exon 4 of 6	ENSP00000337991.5	Q68D10-1
	SPTY2D1	ENST00000536336.5	TSL:2	n.1990A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.51		Loss of MoRF binding (P = 0.0116)
MVP		0.38
MPC		0.78
ClinPred		1.0	D
GERP RS		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.34
Mutation Taster		=51/49	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

hg19: chr11-18633889;