Genetic Variant SERHL2:p.Gln31Lys (chr22-42555006-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014509.5(SERHL2):c.91C>A(p.Gln31Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000048 ( 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: -0.291

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016352266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERHL2	NM_014509.5 link	c.91C>A	p.Gln31Lys	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.91C>A	p.Gln31Lys	missense_variant	Exon 2 of 12	1	NM_014509.5	ENSP00000331376.5		Q9H4I8-1
SERHL2	ENST00000407614.8 link	c.36+55C>A		intron_variant	Intron 2 of 6	1		ENSP00000385691.4		Q9H4I8-3

Frequencies

GnomAD3 genomes

AF:

0.0000364

AC:

AN:

137506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000576

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000675

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

GnomAD3 exomes

AF:

0.000201

AC:

AN:

89402

Hom.:

AF XY:

0.000256

AC XY:

AN XY:

46924

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00144

Gnomad SAS 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:

0.0000482

AC:

AN:

767724

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

397862

show subpopulations

Gnomad4 AFR exome

AF:

0.0000455

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000916

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000537

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000363

AC:

AN:

137600

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

66570

show subpopulations

Gnomad4 AFR

AF:

0.0000574

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000678

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000547

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91C>A (p.Q31K) 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 91, causing the glutamine (Q) at amino acid position 31 to be replaced by a lysine (K). 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

0.081

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.3

DANN

Benign

0.89

DEOGEN2

Benign

0.0080

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.046

Sift

Benign

0.61

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.0010

.;B

Vest4

0.13

MutPred

0.47

Gain of ubiquitination at Q31 (P = 0.03);Gain of ubiquitination at Q31 (P = 0.03);

MVP

0.014

MPC

1.4

ClinPred

0.0022

GERP RS

-5.2

Varity_R

0.071

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over