11-4233299-C-G

Variant names:

• chr11-4233299-C-G
• rs1040724888
• NM_001414002.2:c.12C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001414002.2(SSU72L5):​c.12C>G​(p.Ser4Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S4S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SSU72L5 NM_001414002.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 0 publications found

Genes affected

SSU72L5 (HGNC:43624): (SSU72 like 5) Predicted to enable RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to be involved in dephosphorylation of RNA polymerase II C-terminal domain; mRNA polyadenylation; and termination of RNA polymerase II transcription. Predicted to be part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.635 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414002.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSU72L5	NM_001414002.2	MANE Select	c.12C>G	p.Ser4Ser	synonymous	Exon 1 of 1	NP_001400931.1	A0A1W2PQ64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSU72L5	ENST00000639584.2	TSL:6 MANE Select	c.12C>G	p.Ser4Ser	synonymous	Exon 1 of 1	ENSP00000491949.1	A0A1W2PQ64

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148834 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000238 AC: 1 AN: 421052 Hom.: 0 Cov.: 0 AF XY: 0.00000452 AC XY: 1 AN XY: 221228

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11582

American (AMR) AF: 0.00 AC: 0 AN: 16354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12636

East Asian (EAS) AF: 0.00 AC: 0 AN: 27918

South Asian (SAS) AF: 0.00 AC: 0 AN: 35762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1818

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 253662

Other (OTH) AF: 0.0000410 AC: 1 AN: 24390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000672 AC: 1 AN: 148834 Hom.: 0 Cov.: 24 AF XY: 0.0000138 AC XY: 1 AN XY: 72380

African (AFR) AF: 0.0000247 AC: 1 AN: 40550

American (AMR) AF: 0.00 AC: 0 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4928

South Asian (SAS) AF: 0.00 AC: 0 AN: 4368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67298

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-0.64
PromoterAI		-0.011	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1040724888; hg19: chr11-4254529;