17-63910486-C-G

Variant names:

• chr17-63910486-C-G
• rs200860141
• NM_022579.3:c.240G>C

Variant summary

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

The NM_022579.3(CSHL1):​c.240G>C​(p.Gln80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: CSHL1 NM_022579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 1 publications found

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]

ENSG00000303015 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022579.3. 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
	CSHL1	NM_022579.3	MANE Select	c.240G>C	p.Gln80His	missense	Exon 3 of 5	NP_072101.1	Q14406-1
	CSHL1	NM_001321069.2		c.123G>C	p.Gln41His	missense	Exon 3 of 5	NP_001307998.1
	CSHL1	NM_001321067.2		c.60G>C	p.Gln20His	missense	Exon 2 of 4	NP_001307996.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSHL1	ENST00000309894.6	TSL:5 MANE Select	c.240G>C	p.Gln80His	missense	Exon 3 of 5	ENSP00000309524.5	Q14406-1
	CSHL1	ENST00000346606.10	TSL:1	c.-43G>C		5_prime_UTR	Exon 2 of 4	ENSP00000316360.10	Q14406-4
	CSHL1	ENST00000259003.14	TSL:1	c.74-20G>C		intron	N/A	ENSP00000259003.10	A0A0B4J1R0

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000207 AC: 52 AN: 251490 AF XY: 0.000191

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.0000691 AC: 101 AN: 1461888 Hom.: 0 Cov.: 83 AF XY: 0.0000674 AC XY: 49 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1112010

Other (OTH) AF: 0.000298 AC: 18 AN: 60396

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.000327 AC: 5 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000405 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.73
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.077
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.081	T
MetaSVM	Uncertain	-0.096	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.011	D
Polyphen		0.81	P
Vest4		0.41
MutPred		0.42		Loss of disorder (P = 0.1683)
MVP		0.91
MPC		0.18
ClinPred		0.13	T
GERP RS		2.4
Varity_R		0.24
gMVP		0.30
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200860141; hg19: chr17-61987846;