NM_182577.3:c.574G>C

Variant names:

• chr19-464140-C-G
• rs185731047
• NM_182577.3:c.574G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182577.3(CIMAP1D):​c.574G>C​(p.Ala192Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A192T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.043 (0 hom., cov: 0)
  • Exomes 𝑓: 0.014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 11 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_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029774904).

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.574G>C	p.Ala192Pro	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
	CIMAP1D	NM_001385597.1		c.466G>C	p.Ala156Pro	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
	CIMAP1D	NM_001385598.1		c.250G>C	p.Ala84Pro	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.574G>C	p.Ala192Pro	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
	CIMAP1D	ENST00000382696.7	TSL:1	c.466G>C	p.Ala156Pro	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
	CIMAP1D	ENST00000591681.3	TSL:2	n.*27G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 956 AN: 22544 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.00671

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0464

GnomAD2 exomes AF: 0.173 AC: 1711 AN: 9912 AF XY: 0.178

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.0566

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.220

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0137 AC: 10572 AN: 772392 Hom.: 0 Cov.: 24 AF XY: 0.0157 AC XY: 5808 AN XY: 369016

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0112 AC: 185 AN: 16476

American (AMR) AF: 0.0715 AC: 482 AN: 6742

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 250 AN: 9180

East Asian (EAS) AF: 0.0121 AC: 217 AN: 17890

South Asian (SAS) AF: 0.0978 AC: 2313 AN: 23644

European-Finnish (FIN) AF: 0.0298 AC: 577 AN: 19336

Middle Eastern (MID) AF: 0.0257 AC: 52 AN: 2022

European-Non Finnish (NFE) AF: 0.00929 AC: 6011 AN: 647012

Other (OTH) AF: 0.0161 AC: 485 AN: 30090

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0425 AC: 959 AN: 22562 Hom.: 0 Cov.: 0 AF XY: 0.0424 AC XY: 469 AN XY: 11066

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0391 AC: 245 AN: 6274

American (AMR) AF: 0.0282 AC: 52 AN: 1844

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 29 AN: 538

East Asian (EAS) AF: 0.0541 AC: 46 AN: 850

South Asian (SAS) AF: 0.0695 AC: 42 AN: 604

European-Finnish (FIN) AF: 0.00671 AC: 11 AN: 1640

Middle Eastern (MID) AF: 0.0263 AC: 1 AN: 38

European-Non Finnish (NFE) AF: 0.0492 AC: 510 AN: 10358

Other (OTH) AF: 0.0458 AC: 13 AN: 284

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00800 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.78
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.043
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.16
MPC		0.93
ClinPred		0.039	T
GERP RS		0.90
Varity_R		0.38
gMVP		0.58
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs185731047; hg19: chr19-464140; COSMIC: COSV52745917; COSMIC: COSV52745917;