NM_194285.3:c.1777G>A

Variant names:

• chr11-18612423-C-T
• rs768279652
• NM_194285.3:c.1777G>A

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.1777G>A​(p.Asp593Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,444,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SPTY2D1 NM_194285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257
• Publications: 1 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=0.11337346).
• BS2: High AC in GnomAdExome4 at 9 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.1777G>A	p.Asp593Asn	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.1777G>A	p.Asp593Asn	missense	Exon 4 of 6	ENSP00000337991.5	Q68D10-1
	SPTY2D1	ENST00000536336.5	TSL:2	n.1909G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 249140 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000623 AC: 9 AN: 1444964 Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 2 AN XY: 718690

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.000136 AC: 6 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39332

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099738

Other (OTH) AF: 0.00 AC: 0 AN: 59730

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000412 AC: 5

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	0.15
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.26
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.055
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.36		Loss of stability (P = 0.1528)
MVP		0.22
MPC		0.64
ClinPred		0.81	D
GERP RS		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.22
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: rs768279652; hg19: chr11-18633970;