22-42554037-CA-TT

Variant names:

• chr22-42554037-CA-TT
• NM_014509.5:c.17_18delCAinsTT
• SERHL2 p.Ala6Val

Variant summary

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

The NM_014509.5(SERHL2):​c.17_18delCAinsTT​(p.Ala6Val) 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. A6S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SERHL2 NM_014509.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 publications found

Genes affected

SERHL2 (HGNC:29446): (serine hydrolase like 2) Predicted to enable hydrolase activity. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014509.5. 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
	SERHL2	NM_014509.5	MANE Select	c.17_18delCAinsTT	p.Ala6Val	missense	N/A	NP_055324.2
	SERHL2	NM_001284334.2		c.17_18delCAinsTT	p.Ala6Val	missense	N/A	NP_001271263.1	Q9H4I8-2
	SERHL2	NR_104300.2		n.82_83delCAinsTT		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERHL2	ENST00000327678.10	TSL:1 MANE Select	c.17_18delCAinsTT	p.Ala6Val	missense	N/A	ENSP00000331376.5	Q9H4I8-1
	SERHL2	ENST00000335879.5	TSL:1	c.17_18delCAinsTT	p.Ala6Val	missense	N/A	ENSP00000336578.5	Q9H4I8-2
	SERHL2	ENST00000407614.8	TSL:1	c.17_18delCAinsTT	p.Ala6Val	missense	N/A	ENSP00000385691.4	Q9H4I8-3

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1

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: chr22-42950043;