22-42554962-C-T

Variant names:

• chr22-42554962-C-T
• rs763071757
• NM_014509.5:c.47C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014509.5(SERHL2):​c.47C>T​(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000674 in 148,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERHL2 NM_014509.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• 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]

RRP7BP (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10847148).

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.47C>T	p.Ala16Val	missense	Exon 2 of 12	NP_055324.2
	SERHL2	NM_001284334.2		c.23-270C>T		intron	N/A	NP_001271263.1	Q9H4I8-2
	SERHL2	NR_104300.2		n.112C>T		non_coding_transcript_exon	Exon 2 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERHL2	ENST00000327678.10	TSL:1 MANE Select	c.47C>T	p.Ala16Val	missense	Exon 2 of 12	ENSP00000331376.5	Q9H4I8-1
	SERHL2	ENST00000335879.5	TSL:1	c.23-270C>T		intron	N/A	ENSP00000336578.5	Q9H4I8-2
	SERHL2	ENST00000407614.8	TSL:1	c.36+11C>T		intron	N/A	ENSP00000385691.4	Q9H4I8-3

Frequencies

GnomAD3 genomes AF: 0.00000674 AC: 1 AN: 148358 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000151 AC: 2 AN: 132712 AF XY: 0.0000285

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000339

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 3 AN: 1095934 Hom.: 0 Cov.: 16 AF XY: 0.00000363 AC XY: 2 AN XY: 550348

African (AFR) AF: 0.00 AC: 0 AN: 27674

American (AMR) AF: 0.00 AC: 0 AN: 35424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19666

East Asian (EAS) AF: 0.00 AC: 0 AN: 38864

South Asian (SAS) AF: 0.00 AC: 0 AN: 69366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3264

European-Non Finnish (NFE) AF: 0.00000374 AC: 3 AN: 803120

Other (OTH) AF: 0.00 AC: 0 AN: 48024

GnomAD4 genome AF: 0.00000674 AC: 1 AN: 148358 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 72254

African (AFR) AF: 0.00 AC: 0 AN: 39626

American (AMR) AF: 0.00 AC: 0 AN: 14882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67032

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000170 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.030
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.54	P
Vest4		0.20
MutPred		0.37		Gain of catalytic residue at A16 (P = 0.0902)
MVP		0.014
MPC		1.4
ClinPred		0.34	T
GERP RS		1.4
Varity_R		0.058
gMVP		0.25
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs763071757; hg19: chr22-42950968;