14-24065034-C-G

Variant names:

• chr14-24065034-C-G
• rs748810187
• NM_138360.4:c.3157C>G

Variant summary

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

The NM_138360.4(CARMIL3):​c.3157C>G​(p.Arg1053Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R1053Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CARMIL3 NM_138360.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 1 publications found

Genes affected

CARMIL3 (HGNC:20272): (capping protein regulator and myosin 1 linker 3) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

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=0.1787459).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138360.4. 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
	CARMIL3	NM_138360.4	MANE Select	c.3157C>G	p.Arg1053Gly	missense	Exon 33 of 40	NP_612369.3	Q8ND23-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL3	ENST00000342740.6	TSL:5 MANE Select	c.3157C>G	p.Arg1053Gly	missense	Exon 33 of 40	ENSP00000340467.5	Q8ND23-1
	CARMIL3	ENST00000560349.1	TSL:1	n.1511C>G		non_coding_transcript_exon	Exon 5 of 11
	CARMIL3	ENST00000873684.1		c.3175C>G	p.Arg1059Gly	missense	Exon 33 of 40	ENSP00000543743.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458198 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725462

African (AFR) AF: 0.0000300 AC: 1 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 44052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111026

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0084	T
Eigen	Benign	0.027
Eigen_PC	Benign	-0.0089
FATHMM_MKL	Benign	0.25	N
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.33
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.14
Sift	Benign	0.20	T
Sift4G	Benign	0.32	T
Polyphen		0.96	D
Vest4		0.33
MutPred		0.29		Gain of helix (P = 6e-04)
MVP		0.33
MPC		0.45
ClinPred		0.51	D
GERP RS		2.8
Varity_R		0.079
gMVP		0.60
Mutation Taster		=84/16	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: rs748810187; hg19: chr14-24534243;