7-75496728-T-A

Variant names:

• chr7-75496728-T-A
• rs3973263
• NM_001306141.4:c.434T>A

Variant summary

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

The NM_001306141.4(SPDYE5):​c.434T>A​(p.Met145Lys) 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. 8/12 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. M145R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SPDYE5 NM_001306141.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 0 publications found

Genes affected

SPDYE5 (HGNC:35464): (speedy/RINGO cell cycle regulator family member E5) Predicted to enable protein kinase binding activity. Predicted to be involved in positive regulation of cyclin-dependent protein serine/threonine kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

PMS2P3 (HGNC:):

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=0.11579162).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306141.4. 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
	SPDYE5	NM_001306141.4	MANE Select	c.434T>A	p.Met145Lys	missense	Exon 4 of 9	NP_001293070.1	A6NIY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE5	ENST00000625065.4	TSL:5 MANE Select	c.434T>A	p.Met145Lys	missense	Exon 4 of 9	ENSP00000485398.1	A6NIY4
	PMS2P3	ENST00000845725.1		n.435-5105A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	4.9
DANN	Benign	0.22
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.12	T
PhyloP100		-0.15
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.94	T
Vest4		0.22
MVP		0.072
GERP RS		-0.91
Varity_R		0.31
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3973263; hg19: chr7-75126051;