rs569387737

Variant names:

• chr11-18615000-G-A
• rs569387737
• NM_194285.3:c.1274C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18615000-G-A
• chr11-18615000-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_194285.3(SPTY2D1):​c.1274C>T​(p.Ser425Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SPTY2D1 NM_194285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073596835).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTY2D1	NM_194285.3	c.1274C>T	p.Ser425Phe	missense_variant	Exon 3 of 6	ENST00000336349.6	NP_919261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTY2D1	ENST00000336349.6	c.1274C>T	p.Ser425Phe	missense_variant	Exon 3 of 6	1	NM_194285.3	ENSP00000337991.5
SPTY2D1	ENST00000536336.5	n.1406C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251206 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135850

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461798 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.042
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.031	D
Polyphen		0.022	B
Vest4		0.11
MutPred		0.24		Loss of phosphorylation at S425 (P = 0.007);
MVP		0.043
MPC		0.20
ClinPred		0.19	T
GERP RS		4.0
Varity_R		0.057
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs569387737; hg19: chr11-18636547;