rs757352679

Variant names:

• chr19-757373-C-G
• NM_173481.4:c.427C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-757373-C-G
• chr19-757373-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173481.4(MISP):​c.427C>G​(p.Arg143Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R143C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MISP NM_173481.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

Genes affected

MISP (HGNC:27000): (mitotic spindle positioning) The protein encoded by this gene is an actin-bundling protein involved in determining cell morphology and mitotic progression. The encoded protein is required for the proper positioning of the mitotic spindle. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MISP	NM_173481.4	c.427C>G	p.Arg143Gly	missense_variant	Exon 2 of 5	ENST00000215582.8	NP_775752.1
MISP	XM_011527685.3	c.427C>G	p.Arg143Gly	missense_variant	Exon 2 of 5		XP_011525987.1
MISP	XM_011527686.3	c.427C>G	p.Arg143Gly	missense_variant	Exon 2 of 5		XP_011525988.1
MISP	NR_135168.2	n.61-2536C>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MISP	ENST00000215582.8	c.427C>G	p.Arg143Gly	missense_variant	Exon 2 of 5	1	NM_173481.4	ENSP00000215582.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459818 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.0020
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.52
MutPred		0.73		Loss of helix (P = 0.0104);
MVP		0.66
MPC		0.30
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.51
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-757373;