11-18614805-C-G

Variant names:

• chr11-18614805-C-G
• rs375716843
• NM_194285.3:c.1469G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_194285.3(SPTY2D1):​c.1469G>C​(p.Ser490Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,460,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S490N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SPTY2D1 NM_194285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07834637).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

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.1469G>C	p.Ser490Thr	missense	Exon 3 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.1469G>C	p.Ser490Thr	missense	Exon 3 of 6	ENSP00000337991.5	Q68D10-1
	SPTY2D1	ENST00000536336.5	TSL:2	n.1601G>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460896 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 726666

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111426

Other (OTH) AF: 0.00 AC: 0 AN: 60328

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.0
DANN	Benign	0.83
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.030
Sift	Benign	0.21	T
Sift4G	Benign	0.39	T
Polyphen		0.32	B
Vest4		0.10
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.15
MPC		0.18
ClinPred		0.15	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.075
gMVP		0.17
Mutation Taster		=94/6	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: rs375716843; hg19: chr11-18636352;