11-18611437-T-C

Variant names:

• chr11-18611437-T-C
• rs10128711
• NM_194285.3:c.1964+40A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194285.3(SPTY2D1):​c.1964+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,576,072 control chromosomes in the GnomAD database, including 385,991 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (27689 hom., cov: 33)
  • Exomes 𝑓: 0.70 (358302 hom.)
• Consequence: SPTY2D1 NM_194285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 69 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTY2D1	NM_194285.3	c.1964+40A>G		intron_variant	Intron 5 of 5	ENST00000336349.6	NP_919261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTY2D1	ENST00000336349.6	c.1964+40A>G		intron_variant	Intron 5 of 5	1	NM_194285.3	ENSP00000337991.5

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84992 AN: 151998 Hom.: 27689 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.595

GnomAD2 exomes AF: 0.643 AC: 160544 AN: 249720 AF XY: 0.655

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.634

Gnomad ASJ exome AF: 0.742

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.601

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.678

GnomAD4 exome AF: 0.702 AC: 999354 AN: 1423956 Hom.: 358302 Cov.: 23 AF XY: 0.702 AC XY: 499291 AN XY: 710992

African (AFR) AF: 0.183 AC: 5973 AN: 32658

American (AMR) AF: 0.639 AC: 28388 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 19285 AN: 25870

East Asian (EAS) AF: 0.482 AC: 19024 AN: 39488

South Asian (SAS) AF: 0.631 AC: 53828 AN: 85278

European-Finnish (FIN) AF: 0.609 AC: 32186 AN: 52892

Middle Eastern (MID) AF: 0.721 AC: 4118 AN: 5708

European-Non Finnish (NFE) AF: 0.739 AC: 797106 AN: 1078516

Other (OTH) AF: 0.667 AC: 39446 AN: 59098

GnomAD4 genome AF: 0.559 AC: 84987 AN: 152116 Hom.: 27689 Cov.: 33 AF XY: 0.555 AC XY: 41253 AN XY: 74354

African (AFR) AF: 0.202 AC: 8395 AN: 41496

American (AMR) AF: 0.661 AC: 10105 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2596 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2594 AN: 5160

South Asian (SAS) AF: 0.609 AC: 2942 AN: 4828

European-Finnish (FIN) AF: 0.593 AC: 6265 AN: 10564

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49921 AN: 67990

Other (OTH) AF: 0.591 AC: 1248 AN: 2112

Alfa AF: 0.677 Hom.: 115710

Bravo AF: 0.549

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
DANN	Benign	0.84
PhyloP100		0.032
Mutation Taster		=100/0	polymorphism (auto)

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: rs10128711; hg19: chr11-18632984; COSMIC: COSV60473348; COSMIC: COSV60473348;