11-18612431-T-G

Variant names:

• chr11-18612431-T-G
• rs769366280
• NM_194285.3:c.1769A>C

Variant summary

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

The NM_194285.3(SPTY2D1):​c.1769A>C​(p.Glu590Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E590K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPTY2D1 NM_194285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.95
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1441327).

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.1769A>C	p.Glu590Ala	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.1769A>C	p.Glu590Ala	missense	Exon 4 of 6	ENSP00000337991.5	Q68D10-1
	SPTY2D1	ENST00000536336.5	TSL:2	n.1901A>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458162 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725428

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 85574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109856

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.038
Sift	Benign	0.049	D
Sift4G	Benign	0.19	T
Polyphen		0.82	P
Vest4		0.28
MutPred		0.24		Loss of solvent accessibility (P = 0.0769)
MVP		0.043
MPC		0.68
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.27
Mutation Taster		=64/36	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: rs769366280; hg19: chr11-18633978;