NM_001317.6:c.311T>C

Variant names:

• chr17-63895618-A-G
• NM_001317.6:c.311T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001317.6(CSH1):​c.311T>C​(p.Ile104Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 19)
• Consequence: CSH1 NM_001317.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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]

ENSG00000303015 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.311T>C	p.Ile104Thr	missense	Exon 4 of 5	NP_001308.1	P0DML2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSH1	ENST00000316193.13	TSL:1 MANE Select	c.311T>C	p.Ile104Thr	missense	Exon 4 of 5	ENSP00000316416.8	P0DML2
	CSH1	ENST00000329882.8	TSL:2	c.311T>C	p.Ile104Thr	missense	Exon 4 of 4	ENSP00000333268.8	A6NFB4
	CSH1	ENST00000610991.1	TSL:5	c.44T>C	p.Ile15Thr	missense	Exon 3 of 4	ENSP00000478652.1	A0A087WUG6

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.62	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.046	D
Polyphen		0.51	P
Vest4		0.30
MutPred		0.74		Loss of stability (P = 6e-04)
MVP		0.70
MPC		1.6
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.19
gMVP		0.19

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

Other links and lift over

hg19: chr17-61972978;