19-464103-G-C

Variant names:

• chr19-464103-G-C
• rs1374834190
• NM_182577.3:c.611C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_182577.3(CIMAP1D):​c.611C>G​(p.Pro204Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000334 in 1,195,948 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. P204L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97
• Publications: 0 publications found

Genes affected

CIMAP1D (HGNC:26841): (CIMAP1 family member D) Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182577.3. 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
	CIMAP1D	NM_182577.3	MANE Select	c.611C>G	p.Pro204Arg	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
	CIMAP1D	NM_001385597.1		c.503C>G	p.Pro168Arg	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
	CIMAP1D	NM_001385598.1		c.287C>G	p.Pro96Arg	missense	Exon 4 of 4	NP_001372527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMAP1D	ENST00000315489.5	TSL:1 MANE Select	c.611C>G	p.Pro204Arg	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
	CIMAP1D	ENST00000382696.7	TSL:1	c.503C>G	p.Pro168Arg	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
	CIMAP1D	ENST00000591681.3	TSL:2	n.*64C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000334 AC: 4 AN: 1195948 Hom.: 0 Cov.: 39 AF XY: 0.00000511 AC XY: 3 AN XY: 587134

African (AFR) AF: 0.00 AC: 0 AN: 26404

American (AMR) AF: 0.00 AC: 0 AN: 26426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17796

East Asian (EAS) AF: 0.00 AC: 0 AN: 17376

South Asian (SAS) AF: 0.00 AC: 0 AN: 75126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4164

European-Non Finnish (NFE) AF: 0.00000418 AC: 4 AN: 956222

Other (OTH) AF: 0.00 AC: 0 AN: 45400

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	-0.0030
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-8.4	D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.83		Gain of methylation at P204 (P = 0.0283)
MVP		0.78
MPC		0.90
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.72
gMVP		0.87
Mutation Taster		=76/24	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: rs1374834190; hg19: chr19-464103;