5-154457546-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024632.6(SAP30L):c.*1518C>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 0.0197 in 152,244 control chromosomes in the GnomAD database, including 43 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 0.020 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SAP30L NM_024632.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

SAP30L (HGNC:25663): (SAP30 like) Enables several functions, including non-sequence-specific DNA binding activity, bending; phosphatidylinositol phosphate binding activity; and zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. Part of histone deacetylase complex. [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=-0.87).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0197 (2993/152244) while in subpopulation SAS AF= 0.0429 (207/4822). AF 95% confidence interval is 0.0381. There are 43 homozygotes in gnomad4. There are 1442 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAP30L	NM_024632.6	c.*1518C>T		3_prime_UTR_variant	4/4	ENST00000297109.11
SAP30L	NM_001131062.2	c.*1518C>T		3_prime_UTR_variant	3/3
SAP30L	NM_001131063.2	c.*1518C>T		3_prime_UTR_variant	3/3
SAP30L	NR_024084.2	n.2722C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAP30L	ENST00000297109.11	c.*1518C>T		3_prime_UTR_variant	4/4	1	NM_024632.6	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2997 AN: 152126 Hom.: 43 Cov.: 33

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.00860

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0220

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0197 AC: 2993 AN: 152244 Hom.: 43 Cov.: 33 AF XY: 0.0194 AC XY: 1442 AN XY: 74430

Gnomad4 AFR AF: 0.00553

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.00860

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0221 Hom.: 7

Bravo AF: 0.0190

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.090
Dann	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs148763909; hg19: chr5-153837106;