20-45833923-CAC-TAT

Variant names:

• chr20-45833923-CAC-TAT
• NM_033421.4:c.4_6delCACinsTAT
• SNX21 p.His2Tyr

Variant summary

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

The NM_033421.4(SNX21):​c.4_6delCACinsTAT​(p.His2Tyr) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H2D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX21 NM_033421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 0 publications found

Genes affected

SNX21 (HGNC:16154): (sorting nexin family member 21) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members. The specific function of this protein has not been determined. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

TNNC2 (HGNC:11944): (troponin C2, fast skeletal type) Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]

TNNC2 Gene-Disease associations (from GenCC):

• congenital myopathy 15

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033421.4. 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
	SNX21	NM_033421.4	MANE Select	c.4_6delCACinsTAT	p.His2Tyr	missense	N/A	NP_219489.1	Q969T3-1
	SNX21	NM_152897.3		c.4_6delCACinsTAT	p.His2Tyr	missense	N/A	NP_690857.1	Q969T3-2
	SNX21	NM_001042633.3		c.4_6delCACinsTAT	p.His2Tyr	missense	N/A	NP_001036098.1	A0A0S2Z632

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX21	ENST00000491381.6	TSL:1 MANE Select	c.4_6delCACinsTAT	p.His2Tyr	missense	N/A	ENSP00000418593.1	Q969T3-1
	SNX21	ENST00000342644.9	TSL:1	c.4_6delCACinsTAT	p.His2Tyr	missense	N/A	ENSP00000344586.5	Q969T3-2
	SNX21	ENST00000462307.5	TSL:1	c.4_6delCACinsTAT	p.His2Tyr	missense	N/A	ENSP00000420169.1	Q969T3-3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

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: chr20-44462562;