17-63896134-G-T

Variant names:

• chr17-63896134-G-T
• rs768791010
• NM_001317.6:c.112C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001317.6(CSH1):​c.112C>A​(p.His38Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 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. H38Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSH1 NM_001317.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15903988).

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.112C>A	p.His38Asn	missense	Exon 2 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.112C>A	p.His38Asn	missense	Exon 2 of 5	ENSP00000316416.8	P0DML2
	CSH1	ENST00000329882.8	TSL:2	c.112C>A	p.His38Asn	missense	Exon 2 of 4	ENSP00000333268.8	A6NFB4
	CSH1	ENST00000453363.7	TSL:5	c.112C>A	p.His38Asn	missense	Exon 2 of 3	ENSP00000402517.2	B1A4H2

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD2 exomes AF: 0.0000124 AC: 2 AN: 160674 AF XY: 0.0000115

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000132

Gnomad EAS 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: 0.00000289 AC: 2 AN: 692644 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 354112

African (AFR) AF: 0.00 AC: 0 AN: 13524

American (AMR) AF: 0.00 AC: 0 AN: 23620

Ashkenazi Jewish (ASJ) AF: 0.0000698 AC: 1 AN: 14324

East Asian (EAS) AF: 0.00 AC: 0 AN: 29110

South Asian (SAS) AF: 0.00 AC: 0 AN: 52448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2318

European-Non Finnish (NFE) AF: 0.00000204 AC: 1 AN: 490942

Other (OTH) AF: 0.00 AC: 0 AN: 32716

GnomAD4 genome Cov.: 5

ExAC AF: 0.00000949 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.54
DANN	Benign	0.33
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-1.5	N
PhyloP100		1.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.85	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.61		Loss of catalytic residue at M40 (P = 0.0167)
MVP		0.12
MPC		1.2
ClinPred		0.043	T
GERP RS		0.32
PromoterAI		-0.0090	Neutral
Varity_R		0.11
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs768791010; hg19: chr17-61973494;