19-464068-G-C

Variant names:

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

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>G​(p.Arg216Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,424,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R216C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.1722678).

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>G	p.Arg216Gly	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
	CIMAP1D	NM_001385597.1		c.538C>G	p.Arg180Gly	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
	CIMAP1D	NM_001385598.1		c.322C>G	p.Arg108Gly	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>G	p.Arg216Gly	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
	CIMAP1D	ENST00000382696.7	TSL:1	c.538C>G	p.Arg180Gly	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
	CIMAP1D	ENST00000591681.3	TSL:2	n.*99C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179880 AF XY: 0.0000204

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: 0.0000267

Gnomad OTH exome 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: 0.00 AC: 0 AN: 82362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48144

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

European-Non Finnish (NFE) AF: 0.00000731 AC: 8 AN: 1094942

Other (OTH) AF: 0.00 AC: 0 AN: 58994

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000174 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.043
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.028
Sift	Benign	0.088	T
Sift4G	Uncertain	0.033	D
Polyphen		0.79	P
Vest4		0.31
MutPred		0.38		Loss of MoRF binding (P = 0.0414)
MVP		0.30
MPC		0.73
ClinPred		0.94	D
GERP RS		1.3
Varity_R		0.30
gMVP		0.46
Mutation Taster		=92/8	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;