dbSNP rs946995680: SERHL2:p.Asp49Glu (chr22-42555062-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014509.5(SERHL2):c.147C>A(p.Asp49Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D49N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 15)

Exomes 𝑓: 0.0000088 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SERHL2
NM_014509.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

Publications

0 publications found

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]

SERHL2 links:

RRP7BP (HGNC:):

RRP7BP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24800533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERHL2	NM_014509.5 link	c.147C>A	p.Asp49Glu	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
SERHL2	ENST00000327678.10 link	c.147C>A	p.Asp49Glu	missense_variant	Exon 2 of 12	1	NM_014509.5	ENSP00000331376.5		Q9H4I8-1
SERHL2	ENST00000407614.8 link	c.36+111C>A		intron_variant	Intron 2 of 6	1		ENSP00000385691.4		Q9H4I8-3

Frequencies

GnomAD3 genomes

AF:

0.0000728

AC:

AN:

123700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000297

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

56182

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000199

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000879

AC:

AN:

568788

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

297572

show subpopulations

African (AFR)

AF:

0.000295

AC:

AN:

16936

American (AMR)

AF:

0.00

AC:

AN:

26512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15954

East Asian (EAS)

AF:

0.00

AC:

AN:

34504

South Asian (SAS)

AF:

0.00

AC:

AN:

55026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2264

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

346676

Other (OTH)

AF:

0.00

AC:

AN:

30252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000727

AC:

AN:

123810

Hom.:

Cov.:

AF XY:

0.0000847

AC XY:

AN XY:

59052

show subpopulations

African (AFR)

AF:

0.000295

AC:

AN:

30460

American (AMR)

AF:

0.00

AC:

AN:

12140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3170

East Asian (EAS)

AF:

0.00

AC:

AN:

4158

South Asian (SAS)

AF:

0.00

AC:

AN:

3416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59184

Other (OTH)

AF:

0.00

AC:

AN:

1560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.147C>A (p.D49E) alteration is located in exon 2 (coding exon 2) of the SERHL2 gene. This alteration results from a C to A substitution at nucleotide position 147, causing the aspartic acid (D) at amino acid position 49 to be replaced by a glutamic acid (E). 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

0.33

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

.;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

PhyloP100

2.3

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.097

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.095

T;T

Polyphen

0.98

.;D

Vest4

0.28

MutPred

0.42

Loss of stability (P = 0.1393);Loss of stability (P = 0.1393);

MVP

0.040

MPC

2.0

ClinPred

0.67

GERP RS

1.5

Varity_R

0.25

gMVP

0.32

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over