rs3749893

chr6-116250532-G-Achr6-116250532-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021648.5(TSPYL4):c.*2232C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,228 control chromosomes in the GnomAD database, including 9,410 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 0.33 (9385 hom., cov: 32)
  • Exomes 𝑓: 0.42 (25 hom.)
• Consequence: TSPYL4 NM_021648.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580

Genes affected

TSPYL4 (HGNC:21559): (TSPY like 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in nucleosome assembly. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPYL4	NM_021648.5	c.*2232C>T		3_prime_UTR_variant	1/1	ENST00000420283.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPYL4	ENST00000420283.3	c.*2232C>T		3_prime_UTR_variant	1/1		NM_021648.5	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49856 AN: 151798 Hom.: 9378 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.423 AC: 132 AN: 312 Hom.: 25 Cov.: 0 AF XY: 0.388 AC XY: 76 AN XY: 196

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.328 AC: 49880 AN: 151916 Hom.: 9385 Cov.: 32 AF XY: 0.336 AC XY: 24957 AN XY: 74262

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.338

Alfa AF: 0.355 Hom.: 17239

Bravo AF: 0.318

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.3
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3749893; hg19: chr6-116571695;