1-153112666-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001014450.3(SPRR2F):​c.68G>T​(p.Cys23Phe) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C23S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRR2F NM_001014450.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

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]

ENSG00000301576 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3651959).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014450.3. 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
	SPRR2F	NM_001014450.3	MANE Select	c.68G>T	p.Cys23Phe	missense	Exon 2 of 2	NP_001014450.1	Q96RM1
	SPRR2F	NM_001382255.1		c.68G>T	p.Cys23Phe	missense	Exon 2 of 2	NP_001369184.1	Q96RM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR2F	ENST00000468739.2	TSL:3 MANE Select	c.68G>T	p.Cys23Phe	missense	Exon 2 of 2	ENSP00000418193.1	Q96RM1
	ENSG00000301576	ENST00000779954.1		n.545C>A		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000301557	ENST00000779687.1		n.139-19344C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.098	T
Eigen	Benign	0.061
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.2
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.20
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.47
MutPred		0.080		Loss of glycosylation at P28 (P = 0.1125)
MVP		0.36
MPC		1.0
ClinPred		0.42	T
GERP RS		3.1
Varity_R		0.43
gMVP		0.0038
Mutation Taster		=98/2	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

dbSNP: rs1655622999; hg19: chr1-153085142;