17-63910784-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_022579.3(CSHL1):​c.151A>T​(p.Ile51Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSHL1
NM_022579.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.946
Variant links:
Genes affected
CSHL1 (HGNC:2442): (chorionic somatomammotropin hormone like 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. Although the five genes share a remarkably high degree of sequence identity, they are expressed selectively in different tissues. This particular family member is expressed in placental villi, although it was originally thought to be a pseudogene. In fact, alternative splicing suggests that the majority of the transcripts would be unable to express a secreted protein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.075716466).
BP6
Variant 17-63910784-T-A is Benign according to our data. Variant chr17-63910784-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3497590.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSHL1NM_022579.3 linkc.151A>T p.Ile51Phe missense_variant Exon 2 of 5 ENST00000309894.6 NP_072101.1 Q14406-1I6L999

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSHL1ENST00000309894.6 linkc.151A>T p.Ile51Phe missense_variant Exon 2 of 5 5 NM_022579.3 ENSP00000309524.5 Q14406-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251332
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.0000618
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Oct 01, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
2.6
DANN
Benign
0.89
DEOGEN2
Benign
0.053
.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.59
T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
-1.8
.;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
2.5
N;N
REVEL
Benign
0.21
Sift
Benign
0.28
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
.;B
Vest4
0.18
MutPred
0.53
Loss of stability (P = 0.0512);Loss of stability (P = 0.0512);
MVP
0.33
MPC
0.22
ClinPred
0.075
T
GERP RS
0.62
Varity_R
0.051
gMVP
0.35

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: rs1490049220; hg19: chr17-61988144; API