rs865859982

Variant names:

• chr22-42571188-A-C
• rs865859982
• NM_014509.5:c.716A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-42571188-A-C
• chr22-42571188-A-G

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.716A>C​(p.His239Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H239R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SERHL2 NM_014509.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

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=0.09857091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERHL2	NM_014509.5	c.716A>C	p.His239Pro	missense_variant	Exon 10 of 12	ENST00000327678.10	NP_055324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERHL2	ENST00000327678.10	c.716A>C	p.His239Pro	missense_variant	Exon 10 of 12	1	NM_014509.5	ENSP00000331376.5
SERHL2	ENST00000407614.8	c.176A>C	p.His59Pro	missense_variant	Exon 5 of 7	1		ENSP00000385691.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461394 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111716

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0040
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.43	T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-0.95	T
PhyloP100		-2.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.86	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0030	B;.;B
Vest4		0.26
MutPred		0.68		Loss of MoRF binding (P = 0.0746);.;.;
MVP		0.040
MPC		0.0015
ClinPred		0.22	T
GERP RS		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.44
Mutation Taster		=91/9	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

Publications

LitVar

Other links and lift over

dbSNP: rs865859982; hg19: chr22-42967194;