Variant 11-18614878-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_194285.3(SPTY2D1):c.1396G>C(p.Gly466Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,613,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

SPTY2D1
NM_194285.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Variant links:

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]

SPTY2D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1915324).

BS2

High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTY2D1	NM_194285.3 linkuse as main transcript	c.1396G>C	p.Gly466Arg	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 linkuse as main transcript	c.1396G>C	p.Gly466Arg	missense_variant	3/6	1	NM_194285.3	ENSP00000337991	P1	Q68D10-1
SPTY2D1	ENST00000536336.5 linkuse as main transcript	n.1528G>C		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

250678

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000145

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:

0.000468

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000502

AC:

733

AN:

1461336

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

369

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000134

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:

0.000622

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000315

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000508

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.1396G>C (p.G466R) alteration is located in exon 3 (coding exon 3) of the SPTY2D1 gene. This alteration results from a G to C substitution at nucleotide position 1396, causing the glycine (G) at amino acid position 466 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

M_CAP

Benign

0.027

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

REVEL

Benign

0.19

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.23

MVP

0.093

MPC

0.75

ClinPred

0.22

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.086

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over