1-153040165-G-T

Variant names:

• chr1-153040165-G-T
• rs370349721
• NM_006945.5:c.182C>A

Variant summary

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

The NM_006945.5(SPRR2D):​c.182C>A​(p.Pro61Gln) 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. P61L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRR2D NM_006945.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.775
• Publications: 0 publications found

Genes affected

SPRR2D (HGNC:11264): (small proline rich protein 2D) Predicted to be involved in keratinization. Predicted to act upstream of or within female gonad development and response to estradiol. Located in cytoplasm. [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=0.08143324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006945.5. 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
	SPRR2D	NM_006945.5	MANE Select	c.182C>A	p.Pro61Gln	missense	Exon 2 of 2	NP_008876.3
	SPRR2D	NM_001382248.1		c.182C>A	p.Pro61Gln	missense	Exon 2 of 2	NP_001369177.1	P22532

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRR2D	ENST00000360379.4	TSL:1 MANE Select	c.182C>A	p.Pro61Gln	missense	Exon 2 of 2	ENSP00000353542.3	P22532
	SPRR2D	ENST00000368756.1	TSL:2	c.182C>A	p.Pro61Gln	missense	Exon 3 of 3	ENSP00000357745.1	P22532
	SPRR2D	ENST00000368757.1	TSL:3	c.182C>A	p.Pro61Gln	missense	Exon 2 of 2	ENSP00000357746.1	P22532

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.40
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.78
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.052
Sift4G	Uncertain	0.020	D
Polyphen		0.0050	B
Vest4		0.19
MutPred		0.13		Loss of glycosylation at P61 (P = 0.0122)
MVP		0.12
MPC		0.44
ClinPred		0.063	T
GERP RS		-1.2
Varity_R		0.30
gMVP		0.0017
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: rs370349721; hg19: chr1-153012641;