19-40744607-G-T

Variant names:

• chr19-40744607-G-T
• rs780245332
• NM_198476.5:c.469C>A

Variant summary

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

The NM_001353805.2(ACTMAP):​c.77C>A​(p.Thr26Lys) 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. 11/15 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. T26M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACTMAP NM_001353805.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 6 publications found

Genes affected

ACTMAP (HGNC:24758): (actin maturation protease)

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=0.15485537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353805.2. 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
	ACTMAP	NM_198476.5	MANE Select	c.469C>A	p.Arg157Arg	synonymous	Exon 3 of 6	NP_940878.3	Q5BKX5-1
	ACTMAP	NM_001353805.2		c.77C>A	p.Thr26Lys	missense	Exon 4 of 6	NP_001340734.1	Q5BKX5-3
	ACTMAP	NM_001353809.2		c.469C>A	p.Arg157Arg	synonymous	Exon 3 of 8	NP_001340738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTMAP	ENST00000378313.7	TSL:2 MANE Select	c.469C>A	p.Arg157Arg	synonymous	Exon 3 of 6	ENSP00000367564.2	Q5BKX5-1
	ACTMAP	ENST00000598352.1	TSL:1	c.271C>A	p.Arg91Arg	synonymous	Exon 3 of 6	ENSP00000473024.1	M0R368
	ACTMAP	ENST00000598485.6	TSL:5	c.77C>A	p.Thr26Lys	missense	Exon 4 of 6	ENSP00000469330.2	M0QXR4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250748 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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.5
DANN	Uncertain	0.98
Eigen	Benign	-0.027
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
Sift4G	Benign	0.079	T
Vest4		0.30
MutPred		0.15		Gain of glycosylation at T26 (P = 0.0272)
MVP		0.26
ClinPred		0.17	T
GERP RS		4.8
Mutation Taster		=87/13	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

dbSNP: rs780245332; hg19: chr19-41250512;