14-24064332-G-T

Variant names:

• chr14-24064332-G-T
• NM_138360.4:c.3066G>T
• CARMIL3 p.Leu1022Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_138360.4(CARMIL3):​c.3066G>T​(p.Leu1022Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CARMIL3 NM_138360.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=3.38 with no splicing effect.

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.3066G>T	p.Leu1022Leu	synonymous	Exon 32 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.3066G>T	p.Leu1022Leu	synonymous	Exon 32 of 40	ENSP00000340467.5	Q8ND23-1
	CARMIL3	ENST00000560349.1	TSL:1	n.1420G>T		non_coding_transcript_exon	Exon 4 of 11
	CARMIL3	ENST00000873684.1		c.3084G>T	p.Leu1028Leu	synonymous	Exon 32 of 40	ENSP00000543743.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457488 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724584

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 85296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109778

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		3.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-24533541;