6-116250532-G-A

Variant names:

• chr6-116250532-G-A
• rs3749893
• NM_021648.5:c.*2232C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021648.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL4	NM_021648.5	MANE Select	c.*2232C>T		3_prime_UTR	Exon 1 of 1	NP_067680.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL4	ENST00000420283.3	TSL:6 MANE Select	c.*2232C>T		3_prime_UTR	Exon 1 of 1	ENSP00000410943.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.421 AC: 128 AN: 304

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.158 AC: 6548 AN: 41382

American (AMR) AF: 0.378 AC: 5774 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3466

East Asian (EAS) AF: 0.660 AC: 3411 AN: 5168

South Asian (SAS) AF: 0.540 AC: 2602 AN: 4818

European-Finnish (FIN) AF: 0.420 AC: 4426 AN: 10536

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24762 AN: 67950

Other (OTH) AF: 0.338 AC: 713 AN: 2112

Alfa AF: 0.345 Hom.: 27270

Bravo AF: 0.318

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.47
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3749893; hg19: chr6-116571695;