17-63910252-G-T

Variant names:

• chr17-63910252-G-T
• rs61762513
• NM_022579.3:c.381C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022579.3(CSHL1):​c.381C>A​(p.Thr127Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T127T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSHL1 NM_022579.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.851 with no splicing effect.

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.381C>A	p.Thr127Thr	synonymous	Exon 4 of 5	NP_072101.1	Q14406-1
	CSHL1	NM_022581.3		c.312C>A	p.Thr104Thr	synonymous	Exon 4 of 5	NP_072103.1	Q14406-2
	CSHL1	NM_001321069.2		c.264C>A	p.Thr88Thr	synonymous	Exon 4 of 5	NP_001307998.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSHL1	ENST00000309894.6	TSL:5 MANE Select	c.381C>A	p.Thr127Thr	synonymous	Exon 4 of 5	ENSP00000309524.5	Q14406-1
	CSHL1	ENST00000259003.14	TSL:1	c.195C>A	p.Thr65Thr	synonymous	Exon 4 of 5	ENSP00000259003.10	A0A0B4J1R0
	CSHL1	ENST00000346606.10	TSL:1	c.99C>A	p.Thr33Thr	synonymous	Exon 3 of 4	ENSP00000316360.10	Q14406-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		0.85

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

dbSNP: rs61762513; hg19: chr17-61987612;