chr19-464068-G-A

Variant names:

• chr19-464068-G-A
• rs773763456
• NM_182577.3:c.646C>T

Variant summary

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

The NM_182577.3(CIMAP1D):​c.646C>T​(p.Arg216Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,576,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R216H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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: 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=0.2470628).

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.646C>T	p.Arg216Cys	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
	CIMAP1D	NM_001385597.1		c.538C>T	p.Arg180Cys	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
	CIMAP1D	NM_001385598.1		c.322C>T	p.Arg108Cys	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.646C>T	p.Arg216Cys	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
	CIMAP1D	ENST00000382696.7	TSL:1	c.538C>T	p.Arg180Cys	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
	CIMAP1D	ENST00000591681.3	TSL:2	n.*99C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151638 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000562 AC: 8 AN: 1424704 Hom.: 0 Cov.: 41 AF XY: 0.00000708 AC XY: 5 AN XY: 705846

African (AFR) AF: 0.00 AC: 0 AN: 32748

American (AMR) AF: 0.00 AC: 0 AN: 38774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 37898

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82362

European-Finnish (FIN) AF: 0.0000415 AC: 2 AN: 48144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1094942

Other (OTH) AF: 0.0000339 AC: 2 AN: 58994

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151638 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74070

African (AFR) AF: 0.0000242 AC: 1 AN: 41268

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67846

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000868 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.067
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.056
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.43		Loss of MoRF binding (P = 0.0148)
MVP		0.33
MPC		0.96
ClinPred		0.97	D
GERP RS		1.3
Varity_R		0.24
gMVP		0.45
Mutation Taster		=90/10	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: rs773763456; hg19: chr19-464068;