1-1561821-A-C

Position:

• chr1-1561821-A-C

Variant summary

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

The NM_014188.3(SSU72):​c.224+2952T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,022 control chromosomes in the GnomAD database, including 23,412 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 0.50 (23407 hom., cov: 31)
  • Exomes 𝑓: 0.28 (5 hom.)
• Consequence: SSU72 NM_014188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

Genes affected

SSU72 (HGNC:25016): (SSU72 homolog, RNA polymerase II CTD phosphatase) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in dephosphorylation of RNA polymerase II C-terminal domain and mRNA polyadenylation. Located in cytosol and nucleoplasm. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSU72	NM_014188.3	c.224+2952T>G		intron_variant		ENST00000291386.4	NP_054907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSU72	ENST00000291386.4	c.224+2952T>G		intron_variant		1	NM_014188.3	ENSP00000291386	P1
SSU72	ENST00000359060.5	c.*2714T>G		3_prime_UTR_variant	2/2	2		ENSP00000351955
SSU72	ENST00000378725.3	n.254+2952T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75156 AN: 151816 Hom.: 23331 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.278 AC: 25 AN: 90 Hom.: 5 Cov.: 0 AF XY: 0.242 AC XY: 16 AN XY: 66

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.496 AC: 75298 AN: 151932 Hom.: 23407 Cov.: 31 AF XY: 0.504 AC XY: 37443 AN XY: 74240

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.469

Alfa AF: 0.251 Hom.: 892

Bravo AF: 0.520

Asia WGS AF: 0.796 AC: 2765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3766169; hg19: chr1-1497201;