22-19131878-GC-AT

Variant names:

• chr22-19131878-GC-AT
• NM_053006.5:c.479_480delGCinsAT
• TSSK2 p.Arg160His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_053006.5(TSSK2):​c.479_480delGCinsAT​(p.Arg160His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R160C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSSK2 NM_053006.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896
• Publications: 0 publications found

Genes affected

TSSK2 (HGNC:11401): (testis specific serine kinase 2) TSSK2 belongs to a family of serine/threonine kinases highly expressed in testis (Hao et al., 2004 [PubMed 15044604]).[supplied by OMIM, Mar 2008]

ESS2 (HGNC:16817): (ess-2 splicing factor homolog) This gene is located within the minimal DGS critical region (MDGCR) thought to contain the gene(s) responsible for a group of developmental disorders. These disorders include DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and some familial or sporadic conotruncal cardiac defects which have been associated with microdeletion of 22q11.2. The encoded protein may be a component of C complex spliceosomes, and the orthologous protein in the mouse localizes to the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ENSG00000223461 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053006.5. 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
	TSSK2	NM_053006.5	MANE Select	c.479_480delGCinsAT	p.Arg160His	missense	N/A	NP_443732.3
	ESS2	NM_022719.3	MANE Select	c.*2317_*2318delGCinsAT		3_prime_UTR	Exon 10 of 10	NP_073210.1	Q96DF8
	ESS2	NR_134304.2		n.3836_3837delGCinsAT		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSSK2	ENST00000399635.4	TSL:6 MANE Select	c.479_480delGCinsAT	p.Arg160His	missense	N/A	ENSP00000382544.2	Q96PF2
	ESS2	ENST00000252137.11	TSL:1 MANE Select	c.*2317_*2318delGCinsAT		3_prime_UTR	Exon 10 of 10	ENSP00000252137.6	Q96DF8
	ESS2	ENST00000909110.1		c.*2317_*2318delGCinsAT		3_prime_UTR	Exon 10 of 10	ENSP00000579169.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-19119391;