12-116717840-T-C

Variant names:

• chr12-116717840-T-C
• NM_024738.4:c.588A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_024738.4(SPRING1):​c.588A>G​(p.Gly196Gly) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPRING1 NM_024738.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38
• Publications: 0 publications found

Genes affected

SPRING1 (HGNC:26128): (SREBF pathway regulator in golgi 1) Involved in positive regulation of SREBP signaling pathway. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (REVEL=0.059).
• BP6: Variant 12-116717840-T-C is Benign according to our data. Variant chr12-116717840-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3234399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024738.4. 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
	SPRING1	NM_024738.4	MANE Select	c.588A>G	p.Gly196Gly	synonymous	Exon 5 of 5	NP_079014.1	Q9H741
	SPRING1	NM_001353623.2		c.498A>G	p.Gly166Gly	synonymous	Exon 4 of 4	NP_001340552.1
	SPRING1	NM_001353624.2		c.279A>G	p.Gly93Gly	synonymous	Exon 3 of 3	NP_001340553.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRING1	ENST00000261318.5	TSL:1 MANE Select	c.588A>G	p.Gly196Gly	synonymous	Exon 5 of 5	ENSP00000261318.3	Q9H741
	SPRING1	ENST00000547630.1	TSL:1	n.*287A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000446478.1	F8VPB4
	SPRING1	ENST00000547630.1	TSL:1	n.*287A>G		3_prime_UTR	Exon 4 of 4	ENSP00000446478.1	F8VPB4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454316 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722686

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 84988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108872

Other (OTH) AF: 0.00 AC: 0 AN: 60060

GnomAD4 genome Cov.: 33

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	-0.63
CADD	Benign	9.2
DANN	Benign	0.69
PhyloP100		-1.4
Mutation Taster		=93/7	polymorphism

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

hg19: chr12-117155645;