chr19-464067-C-G

Variant names:

• chr19-464067-C-G
• rs772561825
• NM_182577.3:c.647G>C

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.647G>C​(p.Arg216Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,986 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: 7.0e-7 (0 hom.)
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624
• 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=0.1903387).

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.647G>C	p.Arg216Pro	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
	CIMAP1D	NM_001385597.1		c.539G>C	p.Arg180Pro	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
	CIMAP1D	NM_001385598.1		c.323G>C	p.Arg108Pro	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.647G>C	p.Arg216Pro	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
	CIMAP1D	ENST00000382696.7	TSL:1	c.539G>C	p.Arg180Pro	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
	CIMAP1D	ENST00000591681.3	TSL:2	n.*100G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423986 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 705536

African (AFR) AF: 0.00 AC: 0 AN: 32750

American (AMR) AF: 0.00 AC: 0 AN: 38844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25364

East Asian (EAS) AF: 0.00 AC: 0 AN: 37578

South Asian (SAS) AF: 0.00 AC: 0 AN: 82442

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5422

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094520

Other (OTH) AF: 0.00 AC: 0 AN: 58938

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.099
Eigen_PC	Benign	-0.020
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.62
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.055
Sift	Benign	0.047	D
Sift4G	Uncertain	0.036	D
Polyphen		0.96	D
Vest4		0.25
MutPred		0.42		Loss of MoRF binding (P = 0.0097)
MVP		0.34
MPC		0.95
ClinPred		0.97	D
GERP RS		1.4
Varity_R		0.61
gMVP		0.74
Mutation Taster		=78/22	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: rs772561825; hg19: chr19-464067;