6-109002314-TAG-GAC

Variant names:

• chr6-109002314-TAG-GAC
• NM_014454.3:c.307_309delCTAinsGTC
• SESN1 p.Leu103Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_014454.3(SESN1):​c.307_309delCTAinsGTC​(p.Leu103Val) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SESN1 NM_014454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.84
• Publications: 0 publications found

Genes affected

SESN1 (HGNC:21595): (sestrin 1) This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ARMC2 (HGNC:23045): (armadillo repeat containing 2) Involved in sperm axoneme assembly. Implicated in spermatogenic failure 38. [provided by Alliance of Genome Resources, Apr 2022]

ARMC2 Gene-Disease associations (from GenCC):

• spermatogenic failure 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014454.3. 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
	SESN1	NM_014454.3	MANE Select	c.307_309delCTAinsGTC	p.Leu103Val	missense	N/A	NP_055269.1	Q9Y6P5-2
	SESN1	NM_001199933.2		c.130_132delCTAinsGTC	p.Leu44Val	missense	N/A	NP_001186862.1	Q9Y6P5-1
	SESN1	NM_001199934.2		c.-69_-67delCTAinsGTC		5_prime_UTR	Exon 2 of 10	NP_001186863.1	Q9Y6P5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SESN1	ENST00000436639.7	TSL:1 MANE Select	c.307_309delCTAinsGTC	p.Leu103Val	missense	N/A	ENSP00000393762.2	Q9Y6P5-2
	SESN1	ENST00000356644.7	TSL:1	c.130_132delCTAinsGTC	p.Leu44Val	missense	N/A	ENSP00000349061.7	Q9Y6P5-1
	SESN1	ENST00000302071.6	TSL:1	c.-69_-67delCTAinsGTC		5_prime_UTR	Exon 2 of 10	ENSP00000306734.2	Q9Y6P5-3

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		8.8

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: chr6-109323517;