Genetic Variant CSH1:p.Val211Leu (chr17-63895045-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001317.6(CSH1):c.631G>C(p.Val211Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. V211A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Consequence

CSH1
NM_001317.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Publications

0 publications found

Variant links:

Genes affected

CSH1 (HGNC:2440): (chorionic somatomammotropin hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones and plays an important role in growth control. The gene is located at the growth hormone locus on chromosome 17 along with four other related genes 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. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed mainly in the placenta and utilizes multiple transcription initiation sites. Expression of the identical mature proteins for chorionic somatomammotropin hormones 1 and 2 is upregulated during development, although the ratio of 1 to 2 increases by term. Mutations in this gene result in placental lactogen deficiency and Silver-Russell syndrome. [provided by RefSeq, Jul 2008]

CSH1 links:

ENSG00000303015 (HGNC:):

ENSG00000303015 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35476732).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSH1	NM_001317.6	MANE Select	c.631G>C	p.Val211Leu	missense	Exon 5 of 5	NP_001308.1	P0DML2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSH1	ENST00000316193.13	TSL:1 MANE Select	c.631G>C	p.Val211Leu	missense	Exon 5 of 5	ENSP00000316416.8	P0DML2
CSH1	ENST00000610991.1	TSL:5	c.364G>C	p.Val122Leu	missense	Exon 4 of 4	ENSP00000478652.1	A0A087WUG6
CSH1	ENST00000453363.7	TSL:5	c.346G>C	p.Val116Leu	missense	Exon 3 of 3	ENSP00000402517.2	B1A4H2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.63

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.86

M_CAP

Benign

0.039

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.25

PhyloP100

2.8

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Benign

0.038

Sift4G

Uncertain

0.058

Polyphen

0.091

Vest4

0.23

MutPred

0.42

Gain of helix (P = 0.132)

MVP

0.49

MPC

1.1

ClinPred

0.26

GERP RS

2.6

Varity_R

0.35

gMVP

0.21

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over