19-464140-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182577.3(CIMAP1D):​c.574G>A​(p.Ala192Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000946 in 799,032 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00086 (9 hom.)
• Consequence: CIMAP1D NM_182577.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003979534).
• BP6: Variant 19-464140-C-T is Benign according to our data. Variant chr19-464140-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2411977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

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>A	p.Ala192Thr	missense	Exon 4 of 4	NP_872383.1	Q3SX64-1
	CIMAP1D	NM_001385597.1		c.466G>A	p.Ala156Thr	missense	Exon 3 of 3	NP_001372526.1	Q3SX64-2
	CIMAP1D	NM_001385598.1		c.250G>A	p.Ala84Thr	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>A	p.Ala192Thr	missense	Exon 4 of 4	ENSP00000318029.2	Q3SX64-1
	CIMAP1D	ENST00000382696.7	TSL:1	c.466G>A	p.Ala156Thr	missense	Exon 3 of 3	ENSP00000372143.2	Q3SX64-2
	CIMAP1D	ENST00000591681.3	TSL:2	n.*27G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 91 AN: 23298 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.00163

Gnomad FIN AF: 0.000603

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000186

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000859 AC: 666 AN: 775716 Hom.: 9 Cov.: 24 AF XY: 0.000833 AC XY: 309 AN XY: 370860

African (AFR) AF: 0.0000605 AC: 1 AN: 16530

American (AMR) AF: 0.00 AC: 0 AN: 6816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9260

East Asian (EAS) AF: 0.0339 AC: 606 AN: 17894

South Asian (SAS) AF: 0.000658 AC: 16 AN: 24316

European-Finnish (FIN) AF: 0.000102 AC: 2 AN: 19618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2034

European-Non Finnish (NFE) AF: 0.0000231 AC: 15 AN: 648972

Other (OTH) AF: 0.000859 AC: 26 AN: 30276

GnomAD4 genome AF: 0.00386 AC: 90 AN: 23316 Hom.: 0 Cov.: 0 AF XY: 0.00413 AC XY: 47 AN XY: 11378

African (AFR) AF: 0.000155 AC: 1 AN: 6470

American (AMR) AF: 0.00158 AC: 3 AN: 1896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 574

East Asian (EAS) AF: 0.0943 AC: 82 AN: 870

South Asian (SAS) AF: 0.00163 AC: 1 AN: 614

European-Finnish (FIN) AF: 0.000603 AC: 1 AN: 1658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.000186 AC: 2 AN: 10766

Other (OTH) AF: 0.00 AC: 0 AN: 292

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000933

ExAC AF: 0.0000606 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.78
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.053
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.021	D
Polyphen		0.91	P
Vest4		0.038
MVP		0.11
MPC		0.26
ClinPred		0.63	D
GERP RS		0.90
Varity_R		0.13
gMVP		0.41
Mutation Taster		=96/4	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: COSV105863368; COSMIC: COSV105863368;