NM_173080.3:c.193C>G

Variant names:

• chr1-152972083-C-G
• NM_173080.3:c.193C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173080.3(SPRR4):​c.193C>G​(p.Gln65Glu) 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. 14/20 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)
• Consequence: SPRR4 NM_173080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.765
• Publications: 0 publications found

Genes affected

SPRR4 (HGNC:23173): (small proline rich protein 4) Predicted to be involved in keratinization. Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307055 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055494428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173080.3. 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
	SPRR4	NM_173080.3	MANE Select	c.193C>G	p.Gln65Glu	missense	Exon 2 of 2	NP_775103.1	Q96PI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR4	ENST00000328051.3	TSL:1 MANE Select	c.193C>G	p.Gln65Glu	missense	Exon 2 of 2	ENSP00000332163.2	Q96PI1
	ENSG00000307055	ENST00000823092.1		n.306+66G>C		intron	N/A
	ENSG00000307055	ENST00000823093.1		n.262+66G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.77
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.021
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.21
MutPred		0.11		Gain of ubiquitination at K66 (P = 0.0185)
MVP		0.11
MPC		0.0037
ClinPred		0.11	T
GERP RS		3.2
Varity_R		0.072
gMVP		0.0015
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-152944559;