chr22-42554962-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 12/20 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

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERHL2NM_014509.5 linkc.47C>T p.Ala16Val missense_variant Exon 2 of 12 ENST00000327678.10 NP_055324.2 Q9H4I8-1A0A140VK89

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERHL2ENST00000327678.10 linkc.47C>T p.Ala16Val missense_variant Exon 2 of 12 1 NM_014509.5 ENSP00000331376.5 Q9H4I8-1
SERHL2ENST00000407614.8 linkc.36+11C>T intron_variant Intron 2 of 6 1 ENSP00000385691.4 Q9H4I8-3

Frequencies

GnomAD3 genomes
AF:
0.00000674
AC:
1
AN:
148358
Hom.:
0
Cov.:
26
show subpopulations
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
GnomAD3 exomes
AF:
0.0000151
AC:
2
AN:
132712
Hom.:
0
AF XY:
0.0000285
AC XY:
2
AN XY:
70162
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000374
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000674
AC:
1
AN:
148358
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
72254
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000149
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000170
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.47C>T (p.A16V) alteration is located in exon 2 (coding exon 2) of the SERHL2 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.030
Sift
Benign
0.22
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.54
.;P
Vest4
0.20
MutPred
0.37
Gain of catalytic residue at A16 (P = 0.0902);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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763071757; hg19: chr22-42950968; API