17-63896132-G-T

Variant names:

• chr17-63896132-G-T
• rs747146179
• NM_001317.6:c.114C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001317.6(CSH1):​c.114C>A​(p.His38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSH1 NM_001317.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30590096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSH1	NM_001317.6	c.114C>A	p.His38Gln	missense_variant	Exon 2 of 5	ENST00000316193.13	NP_001308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSH1	ENST00000316193.13	c.114C>A	p.His38Gln	missense_variant	Exon 2 of 5	1	NM_001317.6	ENSP00000316416.8

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000143 AC: 1 AN: 697420 Hom.: 0 Cov.: 9 AF XY: 0.00000280 AC XY: 1 AN XY: 356516

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000422

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 Cov.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	2.0
DANN	Benign	0.58
DEOGEN2	Benign	0.29	T;D;D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.5	.;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.13	B;.;B
Vest4		0.17
MutPred		0.61		Loss of catalytic residue at M40 (P = 0.018);Loss of catalytic residue at M40 (P = 0.018);Loss of catalytic residue at M40 (P = 0.018);
MVP		0.35
MPC		1.2
ClinPred		0.44	T
GERP RS		-0.70
Varity_R		0.27
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747146179; hg19: chr17-61973492;