1-153149947-C-T

Variant names:

• chr1-153149947-C-T
• rs754099877
• NM_001014291.4:c.164G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014291.4(SPRR2G):​c.164G>A​(p.Cys55Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPRR2G NM_001014291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0790
• Publications: 0 publications found

Genes affected

SPRR2G (HGNC:11267): (small proline rich protein 2G) Predicted to be involved in keratinization. Predicted to be located in cornified envelope and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08876616).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014291.4. 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
	SPRR2G	NM_001014291.4	MANE Select	c.164G>A	p.Cys55Tyr	missense	Exon 2 of 2	NP_001014313.1	Q9BYE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR2G	ENST00000368748.5	TSL:1 MANE Select	c.164G>A	p.Cys55Tyr	missense	Exon 2 of 2	ENSP00000357737.4	Q9BYE4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251432 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.42
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.079
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.074
Sift4G	Benign	0.061	T
Polyphen		0.0040	B
Vest4		0.29
MutPred		0.078		Gain of phosphorylation at C55 (P = 0.0148)
MVP		0.25
MPC		0.055
ClinPred		0.053	T
GERP RS		1.4
Varity_R		0.37
gMVP		0.0037
Mutation Taster		=100/0	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: rs754099877; hg19: chr1-153122423;