chr11-18614958-G-C

Position:

• chr11-18614958-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000336349.6(SPTY2D1):​c.1316C>G​(p.Ala439Gly) 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 benign outcome for this variant. 15/21 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)
• Consequence: SPTY2D1 ENST00000336349.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.944

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03388521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTY2D1	NM_194285.3	c.1316C>G	p.Ala439Gly	missense_variant	3/6	ENST00000336349.6	NP_919261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTY2D1	ENST00000336349.6	c.1316C>G	p.Ala439Gly	missense_variant	3/6	1	NM_194285.3	ENSP00000337991	P1
SPTY2D1	ENST00000536336.5	n.1448C>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1316C>G (p.A439G) alteration is located in exon 3 (coding exon 3) of the SPTY2D1 gene. This alteration results from a C to G substitution at nucleotide position 1316, causing the alanine (A) at amino acid position 439 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.00012	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.015
Sift	Benign	0.53	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.28		Gain of catalytic residue at S441 (P = 0.1181);
MVP		0.043
MPC		0.52
ClinPred		0.043	T
GERP RS		3.1
Varity_R		0.024
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18636505;