1-153112666-C-G

Variant names:

• chr1-153112666-C-G
• rs1655622999
• NM_001014450.3:c.68G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014450.3(SPRR2F):​c.68G>C​(p.Cys23Ser) variant causes a missense 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRR2F NM_001014450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

SPRR2F (HGNC:11266): (small proline rich protein 2F) Predicted to be involved in keratinization. Predicted to act upstream of or within response to estradiol. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13356245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRR2F	NM_001014450.3	c.68G>C	p.Cys23Ser	missense_variant	Exon 2 of 2	ENST00000468739.2	NP_001014450.1
SPRR2F	NM_001382255.1	c.68G>C	p.Cys23Ser	missense_variant	Exon 2 of 2		NP_001369184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRR2F	ENST00000468739.2	c.68G>C	p.Cys23Ser	missense_variant	Exon 2 of 2	3	NM_001014450.3	ENSP00000418193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.68G>C (p.C23S) alteration is located in exon 2 (coding exon 1) of the SPRR2F gene. This alteration results from a G to C substitution at nucleotide position 68, causing the cysteine (C) at amino acid position 23 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.70
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.11
Sift4G	Uncertain	0.043	D
Polyphen		0.077	B
Vest4		0.38
MutPred		0.14		Gain of phosphorylation at C23 (P = 0.0024);
MVP		0.32
MPC		0.81
ClinPred		0.13	T
GERP RS		3.1
Varity_R		0.45
gMVP		0.0045

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

Publications

LitVar

Other links and lift over

dbSNP: rs1655622999; hg19: chr1-153085142;