chr17-63896129-A-G

Variant names:

• chr17-63896129-A-G
• NM_001317.6:c.117T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001317.6(CSH1):​c.117T>C​(p.Ala39Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 5)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSH1 NM_001317.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-63896129-A-G is Benign according to our data. Variant chr17-63896129-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2648083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.

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.117T>C	p.Ala39Ala	synonymous	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.117T>C	p.Ala39Ala	synonymous	Exon 2 of 5	ENSP00000316416.8	P0DML2
	CSH1	ENST00000329882.8	TSL:2	c.117T>C	p.Ala39Ala	synonymous	Exon 2 of 4	ENSP00000333268.8	A6NFB4
	CSH1	ENST00000453363.7	TSL:5	c.117T>C	p.Ala39Ala	synonymous	Exon 2 of 3	ENSP00000402517.2	B1A4H2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 30188 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 702412 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 358966

African (AFR) AF: 0.00 AC: 0 AN: 13728

American (AMR) AF: 0.00 AC: 0 AN: 23720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14416

East Asian (EAS) AF: 0.00 AC: 0 AN: 29048

South Asian (SAS) AF: 0.00 AC: 0 AN: 52814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 499582

Other (OTH) AF: 0.00 AC: 0 AN: 33068

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30188 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 14396

African (AFR) AF: 0.00 AC: 0 AN: 3288

American (AMR) AF: 0.00 AC: 0 AN: 3910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 516

East Asian (EAS) AF: 0.00 AC: 0 AN: 768

South Asian (SAS) AF: 0.00 AC: 0 AN: 1208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 122

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16958

Other (OTH) AF: 0.00 AC: 0 AN: 380

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.68
DANN	Benign	0.23
PhyloP100		-1.4
PromoterAI		0.066	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-61973489;